@article {pmid40464500,
year = {2025},
author = {Dedoni, S and Avdoshina, V and Olianas, MC and Onali, P},
title = {Role of Lysophosphatidic Acid in Neurological Diseases: From Pathophysiology to Therapeutic Implications.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {5},
pages = {28245},
doi = {10.31083/FBL28245},
pmid = {40464500},
issn = {2768-6698},
mesh = {Humans ; *Lysophospholipids/metabolism ; *Nervous System Diseases/physiopathology/metabolism/drug therapy ; Animals ; Receptors, Lysophosphatidic Acid/metabolism ; Signal Transduction ; },
abstract = {Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.},
}

Humans
*Lysophospholipids/metabolism
*Nervous System Diseases/physiopathology/metabolism/drug therapy
Animals
Receptors, Lysophosphatidic Acid/metabolism
Signal Transduction

@article {pmid40464332,
year = {2025},
author = {Naim, A and Farooqui, AM and Badruddeen, and Khan, MI and Akhtar, J and Ahmad, A and Islam, A},
title = {The Role of Kinases in Neurodegenerative Diseases: From Pathogenesis to Treatment.},
journal = {The European journal of neuroscience},
volume = {61},
number = {11},
pages = {e70156},
doi = {10.1111/ejn.70156},
pmid = {40464332},
issn = {1460-9568},
mesh = {Humans ; *Neurodegenerative Diseases/enzymology/drug therapy/metabolism ; Animals ; *Protein Kinases/metabolism ; Protein Kinase Inhibitors/therapeutic use ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal loss and dysfunction, with protein kinases playing crucial roles in their pathogenesis. This article explores the involvement of protein kinases in these disorders, focusing on their contributions to disease mechanisms, potential as therapeutic targets and challenges in developing effective treatments. In Alzheimer's disease, kinases such as CDK5, GSK3β and MARK4 are implicated in tau hyperphosphorylation and the formation of neurofibrillary tangles. Kinases also regulate amyloid-β processing and plaque formation. In Parkinson's disease, LRRK2, PINK1 and other kinases contribute to α-synuclein pathology, mitochondrial dysfunction and neuroinflammation. LRRK2 inhibitors and PROTACs have shown promise in preclinical models. Huntington's disease involves altered kinase activity, with CK2, GSK3 and MAPK pathways influencing mutant huntingtin toxicity and aggregation. Kinases are also implicated in less common neurodegenerative diseases, such as ALS and spinocerebellar ataxias. Despite the therapeutic potential of targeting kinases, challenges remain, including the complexity of kinase networks, blood-brain barrier permeability and the lack of robust biomarkers. Emerging technologies, such as covalent inhibitors, targeted protein degradation and combination therapies, offer new avenues for addressing these challenges and developing more effective treatments for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/enzymology/drug therapy/metabolism
Animals
*Protein Kinases/metabolism
Protein Kinase Inhibitors/therapeutic use

@article {pmid40463912,
year = {2025},
author = {Liu, T and Sun, W and Guo, S and Yuan, Z and Zhu, M and Lu, J and Chen, T and Qu, Y and Feng, C and Yang, T},
title = {Role of mitochondrial quality control in neurodegenerative disease progression.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1588645},
pmid = {40463912},
issn = {1662-5102},
abstract = {Neurodegenerative diseases are a diverse group of neurological disorders, in which abnormal mitochondrial function is closely associated with their development and progression. This has generated significant research interest in the field. The proper functioning of mitochondria relies on the dynamic regulation of the mitochondrial quality control system. Key processes such as mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (division/fusion) are essential for maintaining this balance. These processes collectively govern mitochondrial function and homeostasis. Therefore, the mitochondrial quality control system plays a critical role in the onset and progression of neurodegenerative diseases. This article provides a concise overview of the molecular mechanisms involved in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics, explores their interactions, and summarizes current research progress in understanding the mitochondrial quality control system in the context of neurodegenerative diseases.},
}

@article {pmid40460337,
year = {2025},
author = {van Unnik, JWJ and Ing, L and Oliveira Santos, M and McDermott, CJ and de Carvalho, M and van Eijk, RPA},
title = {Remote Monitoring of Amyotrophic Lateral Sclerosis Using Digital Health Technologies: Shifting Toward Digitalized Care and Research?.},
journal = {Neurology},
volume = {105},
number = {1},
pages = {e213738},
doi = {10.1212/WNL.0000000000213738},
pmid = {40460337},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; *Telemedicine ; Wearable Electronic Devices ; Videoconferencing ; Digital Technology ; *Biomedical Technology ; Monitoring, Physiologic/methods ; Digital Health ; },
abstract = {Current care and research pathways for amyotrophic lateral sclerosis (ALS) primarily rely on regularly scheduled visits to specialized centers. These visits provide intermittent clinical information to health care professionals and require patients to travel to the clinic. Digital health technologies enable continuous data collection directly from the patient's home, bringing new opportunities for personalized, timely care and a refined assessment of disease severity in clinical trials. In this review, we summarize the state of the art in digital health technologies for remote monitoring of patients with ALS, ranging from televisits through videoconferencing to sensor-based wearable devices. We explore how these technologies can benefit clinical care and advance treatment development. Despite significant progress, real-world adoption of these technologies remains limited. An overview is provided of the key barriers hindering their widespread implementation and the opportunities to advance the field. Significantly, there is an urgent need for harmonization across stakeholders through consensus guidelines and consortia. These efforts are essential to accelerate progress and harness the full potential of digital health technologies to better meet the needs of patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/diagnosis
*Telemedicine
Wearable Electronic Devices
Videoconferencing
Digital Technology
*Biomedical Technology
Monitoring, Physiologic/methods
Digital Health

@article {pmid40459673,
year = {2025},
author = {Dengri, C and Mayberry, W and Koriesh, A and Nouh, A},
title = {Neurology of Androgens and Androgenic Supplements.},
journal = {Current neurology and neuroscience reports},
volume = {25},
number = {1},
pages = {39},
pmid = {40459673},
issn = {1534-6293},
mesh = {Humans ; *Androgens/metabolism/therapeutic use ; *Nervous System Diseases/drug therapy/metabolism ; *Dietary Supplements ; Receptors, Androgen/metabolism ; Animals ; Testosterone/therapeutic use ; },
abstract = {PURPOSE OF REVIEW: This article explores the intricate relationship between androgens, androgen receptors, and the central nervous system. We examine the role of physiologically derived androgens and androgenic supplements in neurodevelopment and neuroplasticity and delve into the involvement of androgen pathways in the pathogenesis of various neurological disorders.

RECENT FINDINGS: This review highlights the increasing recognition of testosterone and androgen signaling in various neurological conditions, with evidence of both protective and harmful effects depending on dosage and context. Although limited to experimental use, testosterone replacement therapy (TRT) may serve potential benefits in the management of multiple sclerosis, epilepsy, headache, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson disease. On the other hand, androgen-blocking treatments may help alter disease progression in spinal and bulbar muscular atrophy. Testosterone supplementation can have potential adverse events when used at a supratherapeutic level, and prenatal testosterone exposure is believed to contribute to the pathogenesis of neurodevelopmental disease. Additionally, androgen-blocking agents could increase the risk of neurodegenerative conditions, such as Parkinson disease and Alzheimer disease. Despite the above findings, there is no established indication of TRT or androgen-blocking medication in neurological disorders. The body of evidence highlighting the involvement of androgens and androgen receptors (ARs) in pathogenesis of neurological diseases is growing. This includes ongoing research exploring the potential therapeutic targets involving the androgen signaling pathway for management of neurological disorders. Future placebo-controlled clinical trials are essential to determine the efficacy and safety of TRT or androgen-blocking therapies in managing neurological disease.},
}

Humans
*Androgens/metabolism/therapeutic use
*Nervous System Diseases/drug therapy/metabolism
*Dietary Supplements
Receptors, Androgen/metabolism
Animals
Testosterone/therapeutic use

@article {pmid40454774,
year = {2025},
author = {Madrer, N and Perera, ND and Uccelli, NA and Abbondanza, A and Andersen, JV and Carsana, EV and Demmings, MD and Fernandez, RF and de Fragas, MG and Gbadamosi, I and Kulshrestha, D and Lima-Filho, RAS and Marian, OC and Markussen, KH and McGovern, AJ and Neal, ES and Sarkar, S and Šimončičová, E and Soto-Verdugo, J and Yandiev, S and Fernández-Moncada, I},
title = {Neural Metabolic Networks: Key Elements of Healthy Brain Function.},
journal = {Journal of neurochemistry},
volume = {169},
number = {6},
pages = {e70084},
pmid = {40454774},
issn = {1471-4159},
mesh = {Humans ; *Brain/metabolism ; Animals ; *Nerve Net/metabolism ; *Energy Metabolism/physiology ; *Metabolic Networks and Pathways/physiology ; *Neurons/metabolism ; },
abstract = {Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.},
}

Humans
*Brain/metabolism
Animals
*Nerve Net/metabolism
*Energy Metabolism/physiology
*Metabolic Networks and Pathways/physiology
*Neurons/metabolism

@article {pmid40439916,
year = {2025},
author = {Porel, P and Hunjan, G and Kaur, N and Sharma, V and Kaur, M and Mittal, Y and Kaur, R and Aran, KR},
title = {Unlocking the neuroprotective potential of peptide nucleic acids 5 (PNA5) in neurological diseases: molecular mechanisms to therapeutic approaches.},
journal = {Metabolic brain disease},
volume = {40},
number = {5},
pages = {213},
pmid = {40439916},
issn = {1573-7365},
mesh = {Humans ; *Peptide Nucleic Acids/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/drug effects/metabolism ; },
abstract = {Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.},
}

Humans
*Peptide Nucleic Acids/therapeutic use/pharmacology
Animals
*Nervous System Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology
Blood-Brain Barrier/drug effects/metabolism

@article {pmid40036368,
year = {2025},
author = {Ervilha Pereira, P and De Bleecker, JL and Bogaert, E and Dermaut, B},
title = {Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way.},
journal = {Brain : a journal of neurology},
volume = {148},
number = {6},
pages = {1876-1887},
doi = {10.1093/brain/awaf076},
pmid = {40036368},
issn = {1460-2156},
support = {3G0H8318//Research Foundation Flanders/ ; G0AC724N//Research Foundation Flanders/ ; //Funds W. Pyleman and Cremers-Opdebeeck/ ; 2023-J1141680-231086//King Baudouin Foundation/ ; 01N10319//Ghent University Special Research Fund/ ; //Ghent University Fund/ ; },
mesh = {Humans ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; Animals ; *Muscular Diseases/genetics/pathology ; *Prions/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics ; },
abstract = {While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole myopathies. In addition, TAR DNA-binding protein-43 (TDP-43) has been reported to be essential in normal muscle physiology as it is implicated in the formation of so-called amyloid-like myogranules during normal muscle regeneration after injury. However, genetic evidence supporting a primary role for TDP-43 proteinopathy in muscle disease has been missing. In the present review we highlight recent landmark discoveries linking novel pathogenic TDP-43 variants [p.(W385IfsX10) and p.(G376V)] within the prion-like domain with unusual aggregation-propensity and muscle rather than neuronal pathology. We discuss these studies in the context of known TDP-43-related pathways in ALS/FTD pathogenesis and show how they challenge some widely accepted views such as ALS as a pure neurogenic presynaptic neuromuscular disease and the direct correlation between TDP-43 aggregation-propensity and neurotoxicity. Finally, we discuss TDP-43 as part of a growing list of RNA-binding proteins including hnRNPA2B1 and hnRNPA1 as genetic causes of myopathies and relate this to the idea of 'multisystem proteinopathy'.},
}

Humans
*DNA-Binding Proteins/genetics/metabolism
*TDP-43 Proteinopathies/genetics/pathology
Animals
*Muscular Diseases/genetics/pathology
*Prions/genetics/metabolism
Amyotrophic Lateral Sclerosis/genetics

@article {pmid40439808,
year = {2025},
author = {Singh, H and Gupta, R and Gupta, M and Ahmad, A},
title = {Aging-induced alterations in microglial cells and their impact on neurodegenerative disorders.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {515},
pmid = {40439808},
issn = {1573-4978},
mesh = {Humans ; *Microglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Aging/pathology/metabolism ; Animals ; Brain/metabolism/pathology ; Cellular Senescence ; },
abstract = {Senescence causes deterioration in the functioning and physiology of an organism. Microglia, the standing resident immune brain cells transform from neuroprotective to neurotoxic with age. Rapid process motility and cellular migration of microglia in the developing brain, and other characteristics are regarded to be crucial for immunological defense and tissue repair. As they mature, microglia not only differ in their morphology but also in their functioning. However, the exact mechanism related to the atrophies caused by aged microglia or their role in neurodegenerative diseases is still uncertain. The aim of this updated review is to provide insights of how aging microglial cells change and how this influences the development of neurodegenerative diseases. As life expectancy rises, there is an increase in the accumulation of iron, ROS/NOS, protein misfolding and insufficient clearing of debris. This is attributed to the age-dependent alterations in the genes linked to energy metabolism, mitochondrial and lysosome function, and neuroinflammation. Aging microglia often shifts towards a pro-inflammatory state with a reduction of anti-inflammatory cytokines. Aging microglia fail to clear amyloid-beta plaques, accelerates tau-pathology and enhances the chronic neuroinflammation, exacerbating the α-synuclein aggregation. These changes significantly impacted the onset of various neurogenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease etc. However, it is important to note that these microglial aging effects might not be perceived as absolute, due to various limitations such as microglial heterogeneity, intercellular complexity across brain regions and variability in human aging owing to genetic and epigenetic variations. Regardless of this the future perspective of such insights are of immense relevance as novel therapeutic approaches can be formulated if the molecular and cellular mechanisms of aging microglial perturbations are understood. Future research should focus on restoring microglial homeostasis to mitigate the effects of aging on the brain and slowing the progression of neurodegenerative diseases.},
}

Humans
*Microglia/metabolism/pathology
*Neurodegenerative Diseases/metabolism/pathology
*Aging/pathology/metabolism
Animals
Brain/metabolism/pathology
Cellular Senescence

@article {pmid40398193,
year = {2025},
author = {Carra, S and Fabian, B and Taghavi, H and Milanetti, E and Giliberti, V and Ruocco, G and Shepherd, J and Vendruscolo, M and Fuxreiter, M},
title = {Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases.},
journal = {Molecular aspects of medicine},
volume = {103},
number = {},
pages = {101369},
doi = {10.1016/j.mam.2025.101369},
pmid = {40398193},
issn = {1872-9452},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/virology/pathology ; *Protein Aggregates ; *Endogenous Retroviruses/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/virology ; Animals ; *Virion/metabolism ; Protein Folding ; },
abstract = {A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.},
}

Humans
*Neurodegenerative Diseases/metabolism/virology/pathology
*Protein Aggregates
*Endogenous Retroviruses/metabolism/genetics
*Protein Aggregation, Pathological/metabolism/virology
Animals
*Virion/metabolism
Protein Folding

@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*COVID-19/complications/metabolism/virology/pathology
*SARS-CoV-2/physiology
*Neurodegenerative Diseases/metabolism/virology/pathology/etiology
Virus Replication
Animals

@article {pmid40429767,
year = {2025},
author = {Bokulic Panichi, L and Stanca, S and Dolciotti, C and Bongioanni, P},
title = {The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429767},
issn = {1422-0067},
mesh = {Humans ; *Oligodendroglia/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism/etiology ; Animals ; Myelin Sheath/metabolism/pathology ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors-oligodendrocyte progenitor cells (OPCs)-in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity-manifesting as demyelination, hypomyelination, or dysmyelination-have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances.},
}

Humans
*Oligodendroglia/metabolism/pathology
*Neurodegenerative Diseases/pathology/metabolism/etiology
Animals
Myelin Sheath/metabolism/pathology

@article {pmid40428407,
year = {2025},
author = {Škarica, M and Acsadi, G and Živković, SA},
title = {Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.},
journal = {Genes},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/genes16050585},
pmid = {40428407},
issn = {2073-4425},
mesh = {Humans ; *Olivopontocerebellar Atrophies/genetics/pathology ; *Cerebellar Diseases/genetics/pathology ; },
abstract = {Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders.},
}

Humans
*Olivopontocerebellar Atrophies/genetics/pathology
*Cerebellar Diseases/genetics/pathology

@article {pmid40428092,
year = {2025},
author = {Vaccarino, F and Quattrocchi, CC and Parillo, M},
title = {Susceptibility-Weighted Imaging (SWI): Technical Aspects and Applications in Brain MRI for Neurodegenerative Disorders.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
doi = {10.3390/bioengineering12050473},
pmid = {40428092},
issn = {2306-5354},
abstract = {Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) sequence sensitive to substances that alter the local magnetic field, such as calcium and iron, allowing phase information to distinguish between them. SWI is a 3D gradient-echo sequence with high spatial resolution that leverages both phase and magnitude effects. The interaction of paramagnetic (such as hemosiderin and deoxyhemoglobin), diamagnetic (including calcifications and minerals), and ferromagnetic substances with the local magnetic field distorts it, leading to signal changes. Neurodegenerative diseases are typically characterized by the progressive loss of neurons and their supporting cells within the neurovascular unit. This cellular decline is associated with a corresponding deterioration of both cognitive and motor abilities. Many neurodegenerative disorders are associated with increased iron accumulation or microhemorrhages in various brain regions, making SWI a valuable diagnostic tool in clinical practice. Suggestive SWI findings are known in Parkinson's disease, Lewy body dementia, atypical parkinsonian syndromes, multiple sclerosis, cerebral amyloid angiopathy, amyotrophic lateral sclerosis, hereditary ataxias, Huntington's disease, neurodegeneration with brain iron accumulation, and chronic traumatic encephalopathy. This review will assist radiologists in understanding the technical framework of SWI sequences for a correct interpretation of currently established MRI findings and for its potential future clinical applications.},
}

@article {pmid40427919,
year = {2025},
author = {Howarth, NE and Ji, C and Batten, J and Pearce, AJ and Dawes, H and White, AJ and DeLuca, G and Bureau, S and Nowinski, CJ and Miller, MA},
title = {Neurodegenerative Disease and Association Football (NDAF): Systematic Review and Meta-Analysis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
doi = {10.3390/ijerph22050806},
pmid = {40427919},
issn = {1660-4601},
mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/etiology ; *Soccer/injuries ; *Football/injuries ; Risk Factors ; },
abstract = {There is increasing concern that head injuries in Association Football (or soccer) may lead to adverse health outcomes. The aim of this study was to determine whether head impacts or injuries are associated with an increased risk of neurodegenerative disease. We performed a systematic search using PubMed, Embase, and Ovid (up to April 2025). Studies included investigated neurodegenerative diseases in football in comparison to control athletic and general populations. Data were extracted according to PRISMA guidelines. Studies with an odds ratio (OR) were included in the meta-analysis. A total of ten studies were included in this review, of which nine were suitable for meta-analysis from eight cohorts. The risk for developing any neurodegeneration was 1.69 OR (95%CI 1.11 to 2.59; p = 0.01); for Dementia, it was 2.16 OR (95%CI 1.60 to 2.93; p < 0.01; for Motor Neurone Disease (MND), it was 1.39 OR (95%CI 0.67 to 2.53; p = 0.21); for Parkinson's Disease (PD), it was 1.14 OR (95%CI 0.55 to 2.89; p = 0.79). Heterogeneity was reduced following the removal of two studies and the revised risk scores for any neurodegenerative disease; Dementia increased, with that for MND reaching significance, 1.81 OR (95%CI 1.22 to 2.30; p = 0.01), but there remained no association with PD. Evidence suggests that professional football significantly increases the odds of neurodegenerative disease.},
}

Humans
*Neurodegenerative Diseases/epidemiology/etiology
*Soccer/injuries
*Football/injuries
Risk Factors

@article {pmid40427436,
year = {2025},
author = {Minuti, A and Raffaele, I and Scuruchi, M and Lui, M and Muscarà, C and Calabrò, M},
title = {Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/antiox14050554},
pmid = {40427436},
issn = {2076-3921},
support = {Current Research Funds 2025 (RRC-2025-23686388)//Ministero della Salute/ ; },
abstract = {Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.},
}

@article {pmid40426973,
year = {2025},
author = {Ivantsik, O and Exarchos, TP and Vrahatis, AG and Vlamos, P and Krokidis, MG},
title = {Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.},
journal = {Biomedicines},
volume = {13},
number = {5},
pages = {},
doi = {10.3390/biomedicines13051146},
pmid = {40426973},
issn = {2227-9059},
support = {TAEDR-0535850.//This work was partially supported by the European Union-Next Generation EU, Greece 2.0 Na-tional Recovery and Resilience Plan Flagship program TAEDR-0535850./ ; },
abstract = {Protein functionality depends on its proper folding, making protein misfolding crucial for the function of proteins and, by extension, cells and the whole organism. Increasing evidence supports the role of protein misfolding in the pathogenesis of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive disease diagnosed at a prevalence of 5 cases per 100,000, with approximately 2-3 patients per 100,000 diagnosed each year. To date, there is no cure, and the disease usually leads to death within 2 to 5 years from diagnosis. There are two types of the disorder: familial ALS (fALS), accounting for approximately 10% of cases, and sporadic (sALS), accounting for the remaining 90%. The hallmark of ALS, regardless of type, is the protein aggregates found in patients' tissues. This suggests that the disruption of proteostasis plays a critical role in the development of the disease. Herein, we stress the distinct factors that lead to protein misfolding and aggregate formation in ALS. Specifically, we highlight several triggering factors affecting protein misfolding, namely mutations, errors in the processes of protein production and trafficking, and failures of folding and chaperone machinery. Gaining a deeper understanding of protein aggregation will improve our comprehension of disease pathogenesis and potentially uncover new therapeutic approaches.},
}

@article {pmid40422183,
year = {2025},
author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S},
title = {Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.},
journal = {Cells},
volume = {14},
number = {10},
pages = {},
pmid = {40422183},
issn = {2073-4409},
support = {SUMOsolvable//AriSLA/ ; AHA MCA 2022//Giovanni Armenise-Harvard Foundation and AirAlzh/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *Protein Aggregates ; *Protein Aggregation, Pathological/metabolism ; Animals ; Protein Processing, Post-Translational ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*DNA-Binding Proteins/metabolism/genetics
*Frontotemporal Dementia/metabolism/pathology/genetics
*Protein Aggregates
*Protein Aggregation, Pathological/metabolism
Animals
Protein Processing, Post-Translational

@article {pmid40419749,
year = {2025},
author = {Monteiro Neto, JR and de Souza, GF and Dos Santos, VM and de Holanda Paranhos, L and Ribeiro, GD and Magalhães, RSS and Queiroz, DD and Eleutherio, ECA},
title = {SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40419749},
issn = {1559-1182},
support = {201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {Neurons are very susceptible to oxidative stress. They are the major consumers of oxygen in the brain, which is used to provide energy through oxidative phosphorylation, the major source of reactive oxygen species (ROS). In addition, compared to other tissues, neurons have lower levels of catalase and glutathione and increased susceptibility to lipid peroxidation due to the elevated levels of unsaturated fatty acids. These characteristics increasingly emphasize the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) to maintain neuronal redox homeostasis. In the last decade, SOD1 gained additional roles which are also important to the metabolism of neurons. SOD1 controls the production of ROS by the electron transport chain, activates the expression of genes involved in the protection against oxidative stress, and regulates the shift from oxidative to fermentative metabolism involved in astrocyte-neuron metabolic cooperation. Furthermore, impaired interaction between the phosphatase calcineurin and SOD1 seems to result in TDP-43 hyperphosphorylation, the main proteinopathy found in amyotrophic lateral sclerosis (ALS) patients. However, this enzyme is ubiquitously expressed, mutated, and damaged forms of SOD1 cause disease in motor neurons. In this review, we discuss the pivotal functions of SOD1 in neuronal biochemistry and their implications for ALS.},
}

@article {pmid40414644,
year = {2025},
author = {Manusha, S and Varsha, N and Varshini, R and Sivamani, Y and Pokkuluri, KS and Elayaperumal, S},
title = {Altered microbiome influence on the enteric neuromuscular system in amyotrophic lateral sclerosis (ALS).},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {95-123},
doi = {10.1016/bs.irn.2025.04.006},
pmid = {40414644},
issn = {2162-5514},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Enteric Nervous System/physiopathology/microbiology ; *Dysbiosis/physiopathology ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease marked by the degeneration of motor neurons, leading to muscle weakness and paralysis. While the cause of ALS is uncertain, research indicates that changes in the gut microbiome may influence the disease's progression. This chapter explores how alterations in gut microbiota affect the enteric neuromuscular system (ENS) in ALS. In ALS patients, disrupted gut microbiota are linked to the brain-gut axis, impacting both gastrointestinal function and neuronal health. Studies show that microbial changes are associated with inflammation, immune instability, and neurodegeneration, which exacerbate the disease. Gastrointestinal issues like constipation and dysphagia in ALS are tied to ENS dysregulation. Understanding the connections between the gut microbiome, ENS, and central nervous system (CNS) may lead to novel therapies targeting neurodegeneration and microbial dysbiosis in ALS.},
}

*Amyotrophic Lateral Sclerosis/microbiology/physiopathology
Humans
*Gastrointestinal Microbiome/physiology
*Enteric Nervous System/physiopathology/microbiology
*Dysbiosis/physiopathology
Animals

@article {pmid40411245,
year = {2025},
author = {Giacobbe, A and Hiana, J and Wang, O and Benatar, M and Wicks, P and Mascias Cadavid, J and Jhooty, S and McDermott, C and Pattee, G and Bertorini, T and Heiman-Patterson, T and Ratner, D and Barkhaus, P and Carter, G and Jackson, C and Denson, K and Brown, A and Armon, C and Sun, Y and Nguyen, A and Bedlack, R and Li, X},
title = {ALSUntangled #79: alpha-lipoic acid.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2025.2507166},
pmid = {40411245},
issn = {2167-9223},
abstract = {Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It serves as an essential cofactor for enzymatic reactions in mitochondrial energy production, is a potent antioxidant and has anti-inflammatory effects, which are plausible mechanisms in slowing ALS progression. In ALS preclinical studies, ALA slowed motor function decline and improved survival. There were self-reported cases of improved muscle strength in ALS patients when ALA was taken with numerous additional supplements, making it difficult to discern its efficacy. One small, 6-month open-label study showed improved quality of life, fatigue, and mood after participants took it with B vitamins and amino acids for the first 3 months. So far, no clinical trials have been published in people living with amyotrophic lateral sclerosis (PALS). Given the insufficient clinical data, we cannot endorse ALA and will support more research on its efficacy in slowing ALS progression.},
}

@article {pmid40406043,
year = {2025},
author = {Wang, L and Ma, L and Gao, Z and Wang, Y and Qiu, J},
title = {Significance of gene therapy in neurodegenerative diseases.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1515255},
pmid = {40406043},
issn = {1662-4548},
abstract = {Gene therapy is an approach that employs vectors to deliver genetic material to target cells, aiming to correct genes with pathogenic mutations and modulate one or more genes responsible for disease progression. It holds significant value for clinical applications and offers broad market potential due to the large patient population affected by various conditions. For instance, in 2023, the Food and Drug Administration (FDA) approved 55 new drugs, including five specifically for gene therapy targeting hematologic and rare diseases. Recently, with advancements in understanding the pathogenesis and development of neurodegenerative diseases (NDDs), gene therapy has emerged as a promising avenue for treating Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA), particularly in personalized medicine. Notably, the FDA has approved three clinical applications for combating SMA, utilizing viral vectors delivered via intravenous and intrathecal injections. However, gene therapy for other NDDs remains in clinical trials, necessitating improvements in viral vectors, exploration of new vectors, optimization of delivery routes, and further investigation into pathogenesis to identify novel targets. This review discusses recent advancements in gene therapy for NDDs, offering insights into developing new therapeutic strategies.},
}

@article {pmid40355001,
year = {2025},
author = {Ognard, J and El Hajj, G and Verma, O and Ghozy, S and Kadirvel, R and Kallmes, DF and Brinjikji, W},
title = {Advances in endovascular brain computer interface: Systematic review and future implications.},
journal = {Journal of neuroscience methods},
volume = {420},
number = {},
pages = {110471},
doi = {10.1016/j.jneumeth.2025.110471},
pmid = {40355001},
issn = {1872-678X},
mesh = {*Brain-Computer Interfaces/trends ; Animals ; Humans ; *Endovascular Procedures/methods/trends ; *Brain/physiology ; Electrodes, Implanted ; },
abstract = {BACKGROUND: Brain-computer interfaces (BCIs) translate neural activity into real-world commands. While traditional invasive BCIs necessitate craniotomy, endovascular BCIs offer a minimally invasive alternative using the venous system for electrode placement.

NEW METHOD: This systematic review evaluates the technical feasibility, safety, and clinical outcomes of endovascular BCIs, discussing their future implications. A systematic review was conducted per PRISMA guidelines. The search spanned PubMed, Web of Science, and Scopus databases using keywords related to neural interfaces and endovascular approaches. Studies were included if they reported on endovascular BCIs in preclinical or clinical settings. Dual independent screening and extraction focused on electrode material, recording capabilities, safety parameters, and clinical efficacy.

RESULTS: From 1385 initial publications, 26 met the inclusion criteria. Seventeen studies investigated the Stentrode device. Among the 24 preclinical studies, 16 used ovine or rodent models, and 9 addressed engineering or simulation aspects. Two clinical studies reported six ALS patients successfully using an endovascular BCI for digital communication. Preclinical data established the endovascular ovine model, demonstrating stable neural recordings and vascular changes with long-term implantation. Key challenges include thrombosis risk, long-term electrode stability, and anatomical variability.

Endovascular BCI reduced invasiveness, improved safety profiles, with comparable neural recording fidelity to invasive methods, and promising preliminary clinical outcomes in severely paralyzed patients.

CONCLUSIONS: Early results are promising, but clinical data remain scarce. Further research is needed to optimize signal processing, enhance electrode biocompatibility, and refine endovascular procedures for broader clinical applications.},
}

*Brain-Computer Interfaces/trends
Animals
Humans
*Endovascular Procedures/methods/trends
*Brain/physiology
Electrodes, Implanted

@article {pmid40405710,
year = {2025},
author = {Clift, A and Rowen, D and Knox, L and Griffiths, AW and McDermott, CJ},
title = {A Systematic Review of Attributes Influencing Preferences for Treatments and Interventions in People With Amyotrophic Lateral Sclerosis (ALS).},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.28437},
pmid = {40405710},
issn = {1097-4598},
support = {//National Institute for Health and Care Research/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that has no cure, and treatments predominantly focus on improving quality of life. Patient-centred care is central to bringing about meaningful improvements to quality of life. This review addresses the lack of consolidated evidence on what matters most to people with ALS (pwALS) by synthesizing 44 preference-based studies covering six different treatment and intervention categories. Data-based convergent synthesis identified five overarching factors influencing preferences: ease of use, accessibility, making life easier, autonomy, and safety/reliability. Simplifying and enhancing accessibility of treatment delivery across disease stages aligns with the nature of neurodegenerative disorders such as ALS, where function declines as the disease progresses. The value in perceived and real control reflects the profound impact ALS has on an individual's independence. Safety and reliability are crucial for people with ALS and are recognized as fundamental requirements for quality healthcare. The themes identified in this review can inform the attributes of preference elicitation methods. Systematically varying the levels of these attributes elicits quantitative measures of preferences. These findings can be used to inform and develop healthcare policy and clinical practice in ALS care. Specifically, preferences related to drug treatments can then be integrated into target product profiles (TPPs) to align drug development with the needs and values of pwALS. Integrating patient preferences into clinical practice promotes patient-centred care, increasing both patient satisfaction and treatment effectiveness.},
}

@article {pmid40405223,
year = {2025},
author = {Yoonesi, S and Abedi Azar, R and Arab Bafrani, M and Yaghmayee, S and Shahavand, H and Mirmazloumi, M and Moazeni Limoudehi, N and Rahmani, M and Hasany, S and Idjadi, FZ and Aalipour, MA and Gharedaghi, H and Salehi, S and Asadi Anar, M and Soleimani, MS},
title = {Facial expression deep learning algorithms in the detection of neurological disorders: a systematic review and meta-analysis.},
journal = {Biomedical engineering online},
volume = {24},
number = {1},
pages = {64},
pmid = {40405223},
issn = {1475-925X},
mesh = {*Deep Learning ; Humans ; *Nervous System Diseases/diagnosis ; *Facial Expression ; },
abstract = {BACKGROUND: Neurological disorders, ranging from common conditions like Alzheimer's disease that is a progressive neurodegenerative disorder and remains the most common cause of dementia worldwide to rare disorders such as Angelman syndrome, impose a significant global health burden. Altered facial expressions are a common symptom across these disorders, potentially serving as a diagnostic indicator. Deep learning algorithms, especially convolutional neural networks (CNNs), have shown promise in detecting these facial expression changes, aiding in diagnosing and monitoring neurological conditions.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the performance of deep learning algorithms in detecting facial expression changes for diagnosing neurological disorders.

METHODS: Following PRISMA2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published up to August 2024. Data from 28 studies were extracted, and the quality was assessed using the JBI checklist. A meta-analysis was performed to calculate pooled accuracy estimates. Subgroup analyses were conducted based on neurological disorders, and heterogeneity was evaluated using the I[2] statistic.

RESULTS: The meta-analysis included 24 studies from 2019 to 2024, with neurological conditions such as dementia, Bell's palsy, ALS, and Parkinson's disease assessed. The overall pooled accuracy was 89.25% (95% CI 88.75-89.73%). High accuracy was found for dementia (99%) and Bell's palsy (93.7%), while conditions such as ALS and stroke had lower accuracy (73.2%).

CONCLUSIONS: Deep learning models, particularly CNNs, show strong potential in detecting facial expression changes for neurological disorders. However, further work is needed to standardize data sets and improve model robustness for motor-related conditions.},
}

*Deep Learning
Humans
*Nervous System Diseases/diagnosis
*Facial Expression

@article {pmid40403957,
year = {2025},
author = {Zeng, L and Yang, J and Zhang, C and Zhu, J and Zhong, S and Liu, X and Xie, H and Wang, L and Chen, L and Zhong, M and Hua, F and Liang, W},
title = {Miro1: A potential target for treating neurological disorders.},
journal = {Neuroscience},
volume = {577},
number = {},
pages = {228-239},
doi = {10.1016/j.neuroscience.2025.05.019},
pmid = {40403957},
issn = {1873-7544},
abstract = {The Miro1 protein is a member of the mitochondrial Rho GTPase (Miro) protein family and plays a crucial role in regulating the dynamic processes of mitochondria and participating in cellular movement and mitochondrial transport. In the nervous system, it ensures adequate energy supply for normal neuronal function and synaptic transmission. Additionally, Miro1 actively participates in the regulation of mitochondrial quality control and stress responses within neurons. Its primary function is to sense intracellular stress signals to regulate mitochondrial movement and metabolism, thereby adapting to environmental changes. Multiple studies have indicated that the Miro1 protein is associated with the pathogenesis of various neurological disorders, such as Alzheimer's Disease(AD), Parkinson's Disease(PD), and Amyotrophic Lateral Sclerosis(ALS). This article reviews the mechanistic role of Miro1 in these diseases and summarizes the latest research on its involvement in neurological disorders. These efforts aim to provide unified treatment strategies for certain neurological disorders and explore the potential for treating complex neurological diseases.},
}

@article {pmid40403503,
year = {2025},
author = {Dhapola, R and Paidlewar, M and Kumari, S and Sharma, P and Vellingiri, B and Medhi, B and HariKrishnaReddy, D},
title = {cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective.},
journal = {International immunopharmacology},
volume = {159},
number = {},
pages = {114902},
doi = {10.1016/j.intimp.2025.114902},
pmid = {40403503},
issn = {1878-1705},
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD) share key pathological features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, autophagic dysfunction, and DNA damage. By identifying cytosolic DNA and triggering the type I interferon response, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates neuroinflammation. Dysregulated cGAS-STING signaling has been linked to neuroinflammation and neuronal degeneration across multiple neurodegenerative conditions. In many neurodegenerative disorders, neuroinflammation is mediated by the cGAS-STING pathway. Mitochondrial malfunction and impaired autophagy cause cytosolic DNA buildup in Huntington's, Parkinson's, and Alzheimer's diseases, which activates cGAS-STING and drives chronic inflammation. This pathway is triggered by TDP-43 pathology and nucleic acid dysregulation in ALS and FTD, which leads to neuronal destruction. Both central demyelination and peripheral immunological responses are linked to cGAS-STING activation in multiple sclerosis. Various inhibitors, such as RU.521, H-151, and naturally occurring compounds like metformin, potentially attenuate cGAS-STING-mediated neuroinflammation and associated pathologies. H-151 significantly decreased the expression of pro-inflammatory markers in murine macrophage J774 cells activated with cGAMP: TNF-α by 68 %, IFN-β by 84 %, and CXCL10 by 96 %. cGAS-STING inhibitors target neuroinflammation, offering a disease-modifying approach unlike current symptomatic treatments. However, challenges like blood-brain barrier penetration, off-target effects, and immune suppression hinder clinical translation, necessitating optimized drug delivery and immune modulation. With a focus on its potential for future clinical applications, this review explores the role of the cGAS-STING pathway in neurodegeneration and new treatment approaches.},
}

@article {pmid40400898,
year = {2025},
author = {Aziz, S and Anbreen, S and Shahzad, S and Ahmed, MS and Sharma, V and Yang, J and Ali, L},
title = {Investigating nanoparticle's utilization in stem cell therapy for neurological disorders.},
journal = {American journal of stem cells},
volume = {14},
number = {1},
pages = {1-13},
pmid = {40400898},
issn = {2160-4150},
abstract = {Stem cell therapy is a promising area of regenerative medicine, offering potential treatments for various life-threatening disorders. Stem cells are classified based on their differentiation potential into totipotent, pluripotent, and multipotent stem cells. Among them, mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their tissue regeneration capabilities and ability to differentiate into multiple cell types. Stem cells are being explored for treating neurodegenerative disorders like Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). These conditions result from progressive neuronal degeneration, leading to irreversible damage. Challenges such as cell survival, immune rejection, tumor formation, and ethical concerns related to embryonic stem cells need to be addressed. Nanotechnology is emerging as a tool for enhancing stem cell therapy, improving targeted delivery and effectiveness. Nanoparticles possess the ability to create microenvironments as substrates, facilitate targeted administration, and enable real-time, precise imaging of stem cells. This review explores the integration of stem cells and nanotechnology as regenerative medicine tool for neurodegenerative disease treatment, analyzing current strategies and therapeutic approaches. Integrating nanotechnology with stem cell therapy may significantly improve targeted delivery and enhance regenerative outcomes for neurodegenerative disorders.},
}

@article {pmid40398684,
year = {2025},
author = {Naufal, E and Shadbolt, C and Wouthuyzen-Bakker, M and Rele, S and Sahebjada, S and Thuraisingam, S and Babazadeh, S and Choong, PF and Dowsey, MM},
title = {Clinical prediction models to guide treatment of periprosthetic joint infections: A systematic review and meta-analysis.},
journal = {The Journal of hospital infection},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhin.2025.04.035},
pmid = {40398684},
issn = {1532-2939},
abstract = {BACKGROUND: Several clinical prediction models that aim to guide decisions about the management of periprosthetic joint infections (PJI) have been developed. While some models have been recommended for use in clinical settings, their suitability remains uncertain.

METHODS: We systematically reviewed and critically appraised all multivariable prediction models for the treatment of PJI. We searched MEDLINE, EMBASE, Web of Science, and Google Scholar from inception until March 1st, 2024 and included studies that developed or validated models that predict the outcome of PJI. We used PROBAST (Prediction model Risk Of Bias ASsessment Tool) to assess the risk of bias and applicability. Model performance estimates were pooled via random effect meta-analysis.

RESULTS: Thirteen predictive models and seven external validations were identified. Methodological issues were identified in all studies. Pooled estimates indicated that the KLIC (Kidney, Liver, Index surgery, Cemented prosthesis, C-reactive protein) score had fair discriminative performance (pooled c-statistic 0.62, 95% CI 0.55 to 0.69). Both the τ2 (0.02) and I2 (33.4) estimates indicated that between study heterogeneity was minimal. Meta-analysis indicated Shohat et al's model had good discriminative performance (pooled c-statistic 0.74, 95% CI 0.57 to 0.85). Both the τ2 (0.0) and I2 (0.0) indicated that between study heterogeneity was minimal.

CONCLUSIONS: Clinicians should be aware of limitations in the methods used to develop available models to predict outcomes of PJI. As no models have consistently demonstrated adequate performance across external validation studies, it remains unclear if any available models would provide reliable information if used to guide clinical decision-making.},
}

@article {pmid40396445,
year = {2025},
author = {Hu, X and Cheng, J and Yuan, R and Zhou, Y and Rao, J and Wan, Y and Li, Y and Zhang, X and Li, R},
title = {Gold Nanoparticles: Diagnostic and Therapeutic Applications in Neurodegenerative Disorders.},
journal = {Journal of drug targeting},
volume = {},
number = {},
pages = {1-39},
doi = {10.1080/1061186X.2025.2509287},
pmid = {40396445},
issn = {1029-2330},
abstract = {Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases, pose a significant and escalating health challenge in the context of an aging population. Gold nanoparticles (GNPs) have emerged as promising agents in the diagnostic and therapeutic realms of NDDs, due to their unique ability to enhance drug delivery across the blood-brain barrier (BBB). This paper presents a comprehensive review of the application of GNPs in the context of NDDs diagnosis and therapy, highlighting their potential to transform patient management. Additionally, we systematically address the critical challenges associated with the use of GNPs in the treatment and diagnosis of NDDs, focusing on pharmacokinetics and metabolism, toxicity, long-term biocompatibility, regulatory challenges, and cost-effectiveness. Furthermore, we synthesize ongoing clinical studies to provide a holistic perspective on the current state of research in this field. We also explore the prospective trajectories and clinical translational potential of GNPs, which may usher in a new era in the treatment of NDDs.},
}

@article {pmid40395983,
year = {2025},
author = {Beckers, J and Van Damme, P},
title = {The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).},
journal = {Autophagy reports},
volume = {4},
number = {1},
pages = {2474796},
pmid = {40395983},
issn = {2769-4127},
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two extremes of a neurodegenerative disease spectrum characterised by overlapping genetic, clinical, and neuropathological features. This review covers the intricate relationship between both ALS and FTD and defects in the autophagy and endolysosomal pathway as recent evidence has pointed towards alterations in these pathways as being a root cause of disease pathogenesis. Here, we review the current knowledge on the interplay between ALS/FTD and lysosomebased proteostasis pathways and carefully asses the steps of the autophagy and endolysosomal pathways that are impaired by ALS or FTDcausing variants. Finally, we present a comprehensive overview of therapeutic strategies aimed at restoring autophagic and lysosomal function as potential avenues for mitigating the impact of these devastating diseases. Through this review, we aim to enhance the understanding of the pathophysiological mechanisms involving autophagy and/or the endolysosomal system that underlie the ALS-FTD spectrum and underscore the necessity for specific therapeutic approaches that target these shared vulnerabilities.},
}

@article {pmid40395088,
year = {2025},
author = {Zhang, S and Gu, J and Yang, Y and Li, J and Ni, L},
title = {Evolution Trend of Brain Science Research: An Integrated Bibliometric and Mapping Approach.},
journal = {Brain and behavior},
volume = {15},
number = {5},
pages = {e70451},
doi = {10.1002/brb3.70451},
pmid = {40395088},
issn = {2162-3279},
support = {2020Z388//Jiangsu Postdoctoral Research Foundation/ ; //Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee/ ; M202033//Wuxi Health Commission Scientific Research Project/ ; 24CC00903//Beijing Academy of Science and Technology Think Tank Research Project/ ; ZYYB05//Wuxi Administration of Traditional Chinese Medicine/ ; },
mesh = {*Bibliometrics ; Humans ; *Biomedical Research/trends ; *Neurosciences/trends ; *Brain/physiology ; United States ; China ; },
abstract = {BACKGROUND: Brain science research is considered the crown jewel of 21st-century scientific research; the United States, the United Kingdom, and Japan have elevated brain science research to a national strategic level. This study employs bibliometric analysis and knowledge graph visualization to map global trends, research hotspots, and collaborative networks in brain science, providing insights into the field's evolving landscape and future directions.

METHODS: We analyzed 13,590 articles (1990-2023) from the Web of Science Core Collection using CiteSpace and VOSviewer. Metrics included publication volume, co-authorship networks, citation patterns, keyword co-occurrence, and burst detection. Analytical tools such as VOSviewer, CiteSpace, and online bibliometric platforms were employed to facilitate this investigation.

RESULTS: The United States, China, and Germany dominated research output, with China's publications rising from sixth to second globally post-2016, driven by national initiatives like the China Brain Project. However, China exhibited limited international collaboration compared to the United States and European Union. Key journals included Human Brain Mapping and Journal of Neural Engineering, while emergent themes centered on "task analysis," "deep learning," and "brain-computer interfaces" (BCIs). Research clusters revealed three focal areas: (1) Brain Exploration (e.g., fMRI, diffusion tensor imaging), (2) Brain Protection (e.g., stroke rehabilitation, amyotrophic lateral sclerosis therapies), and (3) Brain Creation (e.g., neuromorphic computing, BCIs integrated with AR/VR). Despite China's high output, its influence lagged in highly cited scholars, reflecting a "quantity-over-quality" challenge.

CONCLUSION: Brain science research is in a golden period of development. This bibliometric analysis offers the first comprehensive review, encapsulating research trends and progress in brain science. It reveals current research frontiers and crucial directions, offering a strategic roadmap for researchers and policymakers to navigate countries when planning research layouts.},
}

*Bibliometrics
Humans
*Biomedical Research/trends
*Neurosciences/trends
*Brain/physiology
United States
China

@article {pmid40389567,
year = {2025},
author = {Wu, WL and Gong, XX and Qin, ZH and Wang, Y},
title = {Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
pmid = {40389567},
issn = {1745-7254},
abstract = {Glutamate excitotoxicity is intricately linked to the pathogenesis of neurodegenerative diseases, exerting a profound influence on cognitive functions such as learning and memory in mammals. Glutamate, while crucial for these processes, can lead to neuronal damage and death when present in excessive amounts. Our previous review delved into the cascade of excitotoxic injury events and the underlying mechanisms of excitotoxicity. Building on that foundation, this update summarizes the latest research on the role of excitotoxicity in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as new cutting-edge techniques applied in the study of excitotoxicity. We also explore the mechanisms of action of various excitotoxicity inhibitors and their clinical development status. This comprehensive analysis aims to enhance our understanding of the nexus between excitotoxicity and neurodegenerative diseases, offering valuable insights for therapeutic strategies in these conditions.},
}

@article {pmid40389171,
year = {2025},
author = {Das, D and Das, A and Bhattacharya, K and Koch, KP and Deuri, DJ and Saikia, D and Chanu, NR and Deka, S},
title = {Xanthones as Neuroprotective Agents: A Comprehensive Review of Their Role in the Prevention and Treatment of Neurodegenerative Diseases.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102772},
doi = {10.1016/j.arr.2025.102772},
pmid = {40389171},
issn = {1872-9649},
abstract = {Over the recent years, numerous research efforts have been focused toward xanthones, a class of heterocyclic compounds characterized by a three-ring core structure and a diverse range of biological activities. Despite extensive studies, no xanthone-based molecule has successfully progressed through clinical trials to reach pharmaceutical applications. Xanthones belong to the class of secondary metabolites that exist naturally, found in various plant species, and their structural diversity has been further expanded through synthetic modifications to enhance their pharmacological efficacy. This review provides a comprehensive description of the therapeutic potential of xanthone derivatives within the scope of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuroinflammation. Existing literature has been rigorously examined to highlight the pharmacological relevance of xanthones in these disorders. Additionally, the pathophysiological aspects of each disease are discussed in detail to establish a mechanistic understanding of how xanthone derivatives may exert neuroprotective effects. Furthermore, the SAR of xanthones is explored to elucidate key molecular features responsible for their bioactivity, providing insights into rational drug design. By synthesizing and critically analyzing the existing research, this review is focused in highlighting the therapeutic relevance of xanthones in neurodegenerative diseases and their potential as lead candidates for further drug development.},
}

@article {pmid40388191,
year = {2025},
author = {De Marchi, F and Lombardi, I and Bombaci, A and Diamanti, L and Olivero, M and Perciballi, E and Tornabene, D and Vulcano, E and Ferrari, D and Mazzini, L},
title = {Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1080/14737175.2025.2508781},
pmid = {40388191},
issn = {1744-8360},
abstract = {INTRODUCTION: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce, with riluzole and edaravone offering only limited benefits. The emergence of regenerative medicine, including stem cell therapy, gene-based interventions, and bioengineering strategies, presents a new frontier for ALS treatment.

AREAS COVERED: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving particular focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal stem cells, neural stem cells, and induced pluripotent stem cells; all of which may offer potential neuroprotective and immunomodulatory effects. Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS. The article also covers emerging approaches such as extracellular vesicles, immune-modulating therapies, and bioengineering techniques, including CRISPR-based gene editing and cellular reprogramming, that hold promise for altering disease progression.

EXPERT OPINION: While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted and effective interventions. Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and potentially alter its natural course.},
}

@article {pmid40381433,
year = {2025},
author = {Begh, MZA and Zehravi, M and Bhuiyan, MAK and Molla, MR and Raman, K and Emran, TB and Ullah, MH and Ahmad, I and Osman, H and Khandaker, MU},
title = {Recent advances in stem cell approaches to neurodegeneration: A comprehensive review with mechanistic insight.},
journal = {Pathology, research and practice},
volume = {271},
number = {},
pages = {156013},
doi = {10.1016/j.prp.2025.156013},
pmid = {40381433},
issn = {1618-0631},
abstract = {The progressive nature of neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, presents substantial problems because current treatments are still obscure. Stem cell-based treatments are emerging as a viable solution to address the significant gaps in treating these severe diseases. This study provides a comprehensive analysis of the latest advancements in stem cell research, focusing on the treatment of NDs. Various types of stem cells, such as adult, induced pluripotent, and embryonic stem cells, and their potential applications in immunomodulation, neurotrophic factor release, and neuronal development are also discussed. Recent clinical studies reveal outcomes, challenges, and solutions, with advancements in disease-specific neural cell production, gene editing, and improved stem cell transplantation transport strategies. The review discussed future perspectives on developing more effective stem cell-based interventions. Biomaterials are being used for cell distribution and personalized medicine techniques to improve treatment outcomes, while exploring stem cell treatments for NDs and identifying areas for further research.},
}

@article {pmid40378897,
year = {2025},
author = {Fontanelli, L and Nisini, N and Pirola, S and Recchia, FA},
title = {Neuromuscular and cardiac organoids and assembloids: Advanced platforms for drug testing.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108876},
doi = {10.1016/j.pharmthera.2025.108876},
pmid = {40378897},
issn = {1879-016X},
abstract = {The inherent technical difficulties, ethical/regulatory issues and costs of experimental studies in animal models is prompting investigators to replace as much as possible living organisms with in vitro physiological models named organoids and assembloids. Generated from induced pluripotent stem cells, these three-dimensional structures approximate the complexity of tissues and their interactions, enabling personalized disease modelling and drug testing. The integration of multiple components in assembloids further enhances their predictive value for multi-system interactions and toxicities. This review describes how neuromuscular organoids, incorporating functional neuromuscular junctions and contractile muscle tissue, have been used to replicate, in vitro, complex neuromuscular morpho-functional structures, offering very valuable platforms to study molecular mechanisms and drug effects in models of incurable diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. In the cardiological field, cardiac organoids and assembloids are proving reliable models for testing drug effects at molecular, morphological, electrophysiological and mechanical level. Recently, the integration of neuronal components into cardiac organoids has provided a potential approach to investigate autonomic function, a fundamental aspect of many neurological, neuromuscular and cardiac diseases. Challenges and limitations still remain, including the non-uniform differentiation protocols across studies, the incomplete maturation of cell phenotypes, and the lack of integrated pharmacokinetic modelling. We discussed some future developments aimed at overcoming such hurdles. Despite their current limitations, organoids and assembloids clearly hold great promises and will help advancing many fields of biomedicine.},
}

@article {pmid40374790,
year = {2025},
author = {Verma, KK and Gaur, PK and Gupta, SL and Lata, K and Kaushik, R and Sharma, V},
title = {Metabolomics: a new frontier in neurodegenerative disease biomarker discovery.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {21},
number = {3},
pages = {67},
pmid = {40374790},
issn = {1573-3890},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Biomarkers/metabolism/analysis ; *Metabolomics/methods ; Animals ; },
abstract = {BACKGROUND: Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.

AIM OF REVIEW: This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).

Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.},
}

Humans
*Neurodegenerative Diseases/metabolism/diagnosis
*Biomarkers/metabolism/analysis
*Metabolomics/methods
Animals

@article {pmid40364088,
year = {2025},
author = {Plotti, F and Martinelli, A and Terranova, C and De Cicco Nardone, C and Montera, R and Luvero, D and Guzzo, F and Di Donato, V and Cundari, GB and Manco, S and Angioli, R},
title = {Laparoscopic Lateral Suspension (LLS) for Pelvic Organ Prolapse (POP): Update and Systematic Review of Prospective and Randomised Trials.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364088},
issn = {2077-0383},
abstract = {Background: Pelvic organ prolapse (POP) significantly impacts women's quality of life, especially in postmenopausal patients. Although laparoscopic sacrocolpopexy (LSC) is the gold standard for advanced apical prolapse, its complexity and risk of complications have led to alternative approaches like laparoscopic lateral suspension (LLS), a minimally invasive technique with promising results. Methods: A comprehensive search using PubMed databases was performed. The search was conducted from June 2024 to September 2024. The search string used was as follows: (pelvic organ prolapse) AND (lateral suspension) OR (laparoscopic lateral suspension). We included randomized controlled trials, prospective cohort studies, prospective observational studies, and case studies. We excluded retrospective studies, small case series, case reports, and articles not published in English. All selected articles were screened based on the titles and abstracts. Relevant data were extracted and tabulated. Results: An overall number of 12 studies were included in our analysis. LLS demonstrated high anatomical success rates: 91.15% for the anterior, 94.95% for the central, and 86.55% for the posterior compartments. The randomized controlled studies exhibit comparable effectiveness between both methods (LLS vs. LSC) and LLS appears to be the best option for anterior repair or anterior-apical repair. Patient satisfaction rates exceeded 90%, with reduced operative times (123 ± 33 min and 193 ± 55.6 min for ALS and ASC, respectively). According to the Claiven-Dindo scale, 0.17% of postoperative complications were graded more than III. The rate of mesh erosion was 0% to 10%. The technique showed particular benefit for uterine preservation and in obese patients but was less effective for severe posterior prolapse. Conclusions: Laparoscopic lateral suspension offers a safe, effective alternative for POP management, with significant anatomical and functional benefits. Its minimally invasive nature, shorter surgery time, and high satisfaction rates make it suitable for tailored patient care. Further studies should standardize evaluation metrics and assess long-term outcomes. The review was not registered. No funding was received. The authors declare no competing interests.},
}

@article {pmid40362582,
year = {2025},
author = {Kitaoka, Y and Uchihashi, T and Kawata, S and Nishiura, A and Yamamoto, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S and Spigelman, I and Seki, S},
title = {Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362582},
issn = {1422-0067},
support = {24K13154//Japan Society for the Promotion of Science/ ; 21K10091//Japan Society for the Promotion of Science/ ; 24K13113//Japan Society for the Promotion of Science/ ; 23K09351//Japan Society for the Promotion of Science/ ; 24K13112//Japan Society for the Promotion of Science/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; *Artificial Intelligence ; Proteomics/methods ; Neuroimaging/methods ; Deep Learning ; },
abstract = {Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), present significant challenges owing to their complex pathologies and a lack of curative treatments. Early detection and reliable biomarkers are critical but remain elusive. Artificial intelligence (AI) has emerged as a transformative tool, enabling advancements in biomarker discovery, diagnostic accuracy, and therapeutic development. From optimizing clinical-trial designs to leveraging omics and neuroimaging data, AI facilitates understanding of disease and treatment innovation. Notably, technologies such as AlphaFold and deep learning models have revolutionized proteomics and neuroimaging, offering unprecedented insights into ALS pathophysiology. This review highlights the intersection of AI and ALS, exploring the current state of progress and future therapeutic prospects.},
}

*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism
Humans
*Biomarkers/metabolism
*Artificial Intelligence
Proteomics/methods
Neuroimaging/methods
Deep Learning

@article {pmid40362512,
year = {2025},
author = {Chong, ZZ and Souayah, N},
title = {Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362512},
issn = {1422-0067},
mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; DNA Repeat Expansion ; Animals ; Mutation ; Autophagy ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal adult neurodegenerative disorder. Since no cure has been found, finding effective therapeutic targets for ALS remains a major challenge. Gene C9orf72 mutations with the formation of hexanucleotide repeat (GGGGCC) expansion (HRE) have been considered the most common genetic pathogenesis of ALS. The literature review indicates that the C9orf72 HRE causes both the gain-of-function toxicity and loss of function of C9ORF72. The formation of RNA foci and dipeptide repeats (DPRs) resulting from HRE is responsible for toxic function gain. The RNA foci can interfere with RNA processing, while DPRs directly bind to and sequester associated proteins to disrupt processes of rRNA synthesis, mRNA translation, autophagy, and nucleocytoplasmic transport. The mutations of C9orf72 and HRE result in the loss of functional C9ORF72. Under physiological conditions, C9ORF72 binds to Smith-Magenis chromosome region 8 and WD repeat-containing protein and forms a protein complex. Loss of C9ORF72 leads to autophagic impairment, increased oxidative stress, nucleocytoplasmic transport impairment, and inflammatory response. The attempted treatments for ALS have been tried by targeting C9orf72 HRE; however, the outcomes are far from satisfactory yet. More studies should be performed on pharmacological and molecular modulators against C9orf72 HRE to evaluate their efficacy by targeting HRE.},
}

*C9orf72 Protein/genetics/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy
Humans
DNA Repeat Expansion
Animals
Mutation
Autophagy

@article {pmid40133096,
year = {2025},
author = {Shenouda, M and McKeever, PM and Robertson, J},
title = {The long and the short of TDP-43.},
journal = {Trends in neurosciences},
volume = {48},
number = {5},
pages = {313-314},
doi = {10.1016/j.tins.2025.03.003},
pmid = {40133096},
issn = {1878-108X},
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Protein Isoforms/metabolism/genetics ; },
abstract = {In a recent study, Dykstra and colleagues show that shortened TAR DNA Binding Protein 43 (sTDP-43) isoforms are generated as by-products of TDP-43 autoregulation. sTDP-43 levels are regulated through nonsense-mediated decay and proteasomal and autophagic degradation, and elicit toxicity through dominant negative effects on TDP-43 splicing activity. These results identify mechanisms contributing to sTDP-43 accumulation and toxicity in disease.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
Animals
Protein Isoforms/metabolism/genetics

@article {pmid40362304,
year = {2025},
author = {Shiryaeva, O and Tolochko, C and Alekseeva, T and Dyachuk, V},
title = {Targets and Gene Therapy of ALS (Part 1).},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
doi = {10.3390/ijms26094063},
pmid = {40362304},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/genetics/pathology ; *Genetic Therapy/methods ; Animals ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; Gene Editing ; RNA-Binding Protein FUS/genetics ; Oligonucleotides, Antisense/therapeutic use ; CRISPR-Cas Systems ; DNA-Binding Proteins/genetics ; RNA Interference ; MicroRNAs/genetics ; Disease Models, Animal ; RNA, Small Interfering/genetics ; Motor Neurons/metabolism/pathology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons, which causes muscle atrophy. Genetic forms of ALS are recorded only in 10% of cases. However, over the past decade, studies in genetics have substantially contributed to our understanding of the molecular mechanisms underlying ALS. The identification of key mutations such as SOD1, C9orf72, FUS, and TARDBP has led to the development of targeted therapy that is gradually being introduced into clinical trials, opening up a broad range of opportunities for correcting these mutations. In this review, we aimed to present an extensive overview of the currently known mechanisms of motor neuron degeneration associated with mutations in these genes and also the gene therapy methods for inhibiting the expression of their mutant proteins. Among these, antisense oligonucleotides, RNA interference (siRNA and miRNA), and gene-editing (CRISPR/Cas9) methods are of particular interest. Each has shown its efficacy in animal models when targeting mutant genes, whereas some of them have proven to be efficient in human clinical trials.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/genetics/pathology
*Genetic Therapy/methods
Animals
Superoxide Dismutase-1/genetics
C9orf72 Protein/genetics
Mutation
Gene Editing
RNA-Binding Protein FUS/genetics
Oligonucleotides, Antisense/therapeutic use
CRISPR-Cas Systems
DNA-Binding Proteins/genetics
RNA Interference
MicroRNAs/genetics
Disease Models, Animal
RNA, Small Interfering/genetics
Motor Neurons/metabolism/pathology

@article {pmid40360341,
year = {2025},
author = {Lin, W and Huang, C and Tan, Z and Xu, H and Wei, W and Wang, L},
title = {Cu[II]-bis(thioureido) Complex: A Potential Radiotracer for Detecting Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases.},
journal = {Seminars in nuclear medicine},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.semnuclmed.2025.03.008},
pmid = {40360341},
issn = {1558-4623},
abstract = {Neurodegenerative diseases, characterized by progressive neuronal degeneration and associated with neuroinflammation and oxidative stress, present significant challenges in diagnosis and treatment. This review explores the potential of copper(II)-bis(thiosemicarbazone) complexes, particularly Cu-ATSM, as a dual-purpose radiopharmaceutical for imaging and therapeutic interventions. Cu-ATSM exhibits unique redox-dependent retention in pathological microenvironments, driven by mitochondrial dysfunction and hyper-reductive states, which enables the noninvasive detection of oxidative stress via positron emission tomography (PET). Preclinical studies demonstrate its efficacy in mitigating neuroinflammation by suppressing glial activation, reducing the secretion of pro-inflammatory cytokines (e.g., TNF-α, MCP-1), and increasing the expression of neuroprotective metallothionein-1 (MT1). Some Clinical research reveals elevated [64]Cu-ATSM uptake in Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients, correlating with disease severity and regional oxidative stress markers. Furthermore, Cu-ATSM derivatives show promise in modulating blood-brain barrier (BBB) permeability, enhancing amyloid-β clearance, and restoring copper homeostasis in ALS models. Despite these advances, limitations such as small cohort sizes and heterogeneity in clinical studies underscore the need for larger-scale validation. Multimodal imaging integrating PET and MRI, alongside novel structural analogs targeting Aβ plaques and redox imbalances, emerges as a strategic direction for future research. Collectively, Cu-ATSM represents a transformative tool for elucidating neuropathological mechanisms and advancing therapeutic strategies in neurodegenerative disorders.},
}

@article {pmid40353906,
year = {2025},
author = {Kleinerova, J and Querin, G and Pradat, PF and Siah, WF and Bede, P},
title = {New developments in imaging in ALS.},
journal = {Journal of neurology},
volume = {272},
number = {6},
pages = {392},
pmid = {40353906},
issn = {1432-1459},
support = {JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; *Neuroimaging/methods/trends ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging ; },
abstract = {Neuroimaging in ALS has contributed considerable academic insights in recent years demonstrating genotype-specific topological changes decades before phenoconversion and characterising longitudinal propagation patterns in specific phenotypes. It has elucidated the radiological underpinnings of specific clinical phenomena such as pseudobulbar affect, apathy, behavioural change, spasticity, and language deficits. Academic concepts such as sexual dimorphism, motor reserve, cognitive reserve, adaptive changes, connectivity-based propagation, pathological stages, and compensatory mechanisms have also been evaluated by imaging. The underpinnings of extra-motor manifestations such as cerebellar, sensory, extrapyramidal and cognitive symptoms have been studied by purpose-designed imaging protocols. Clustering approaches have been implemented to uncover radiologically distinct disease subtypes and machine-learning models have been piloted to accurately classify individual patients into relevant diagnostic, phenotypic, and prognostic categories. Prediction models have been developed for survival in symptomatic patients and phenoconversion in asymptomatic mutation carriers. A range of novel imaging modalities have been implemented and 7 Tesla MRI platforms are increasingly being used in ALS studies. Non-ALS MND conditions, such as PLS, SBMA, and SMA, are now also being increasingly studied by quantitative neuroimaging approaches. A unifying theme of recent imaging papers is the departure from describing focal brain changes to focusing on dynamic structural and functional connectivity alterations. Progressive cortico-cortical, cortico-basal, cortico-cerebellar, cortico-bulbar, and cortico-spinal disconnection has been consistently demonstrated by recent studies and recognised as the primary driver of clinical decline. These studies have led the reconceptualisation of ALS as a "network" or "circuitry disease".},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology
*Neuroimaging/methods/trends
*Brain/diagnostic imaging
Magnetic Resonance Imaging

@article {pmid40350993,
year = {2025},
author = {Vedeler, A and Tartaglia, GG and Pastore, A},
title = {Annexin, a Protein for All Seasons: From Calcium Dependent Membrane Metabolism to RNA Recognition.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e70019},
doi = {10.1002/bies.70019},
pmid = {40350993},
issn = {1521-1878},
support = {ASTRA_855923//ERC / ; PNRRCN00000041andEPNRRCN3//Piano Nazionale di Ripresa e Resilienza of Italian MUR/ ; IVBM4PAP_101098989//EIC Pathfinder/ ; ARUK_PG2019B-020//ARUK / ; },
abstract = {Annexins are a protein family well known to bind to phospholipids in a calcium-dependent way. They are involved in several different crucial cellular processes such as cell division, calcium signaling, membrane repair, vesicle trafficking, and apoptosis. Although RNA binding for some members of the family was reported long ago, it was only recently that it was shown that a common feature of the family is also the ability to bind RNA, a discovery that has added significantly to our perception of the cellular role of these proteins. In the present review, we discuss the properties of annexins under an updated light and the current knowledge on the RNA binding properties of annexins. We then focus specifically on annexin A11, because this is a less characterized member of the family but, at the same time, a potentially important component of the mRNA transport machinery in neurons. We hope to offer to the reader a more complete picture of the annexins' binding properties and new tools to evaluate the multifaceted functions of this important protein family.},
}

@article {pmid40350723,
year = {2025},
author = {Kuznetsova, DR and Kutlubaev, MA and Pervushina, EV},
title = {[Oculomotor disorders in patients with amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {125},
number = {4},
pages = {7-12},
doi = {10.17116/jnevro20251250417},
pmid = {40350723},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; Saccades ; Eye Movements ; },
abstract = {Oculomotor disorders are not typical manifestations of amyotrophic lateral sclerosis (ALS). Occasionally, this disease is associated with vertical gaze paresis, presenting a distinct type as «ALS+progressive supranuclear palsy». Studies using eye-tracking methods have revealed a variety of subclinical oculomotor disorders in this disease. These disorders can manifest as changes in reflex and voluntary saccades, antisaccades, smooth tracking eye movements, and fixations. A significant association between oculomotor disorders and clinical manifestations of ALS was reported. The occurrence of oculomotor disorders indicates the involvement of broader neuroanatomical structures, including the prefrontal cortex and basal ganglia. The lack of consistency in the data from different studies and their limited number emphasize the need for further research in this area.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
*Ocular Motility Disorders/etiology/physiopathology/diagnosis
Saccades
Eye Movements

@article {pmid40350633,
year = {2025},
author = {Ishiura, H},
title = {[Genetics of Motor Neuron Diseases and Hereditary Spastic Paraplegia].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {77},
number = {5},
pages = {481-491},
doi = {10.11477/mf.188160960770050481},
pmid = {40350633},
issn = {1881-6096},
mesh = {Humans ; *Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy ; *Motor Neuron Disease/genetics/diagnosis ; },
abstract = {Motor neuron diseases encompass a range of phenotypes, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and spinal muscular atrophy (SMA). Related conditions include spinal and bulbar muscular atrophy (SBMA) and hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). Hereditary spastic paraplegia (HSP)-a group of disorders primarily affecting the corticospinal tract-also exhibits diverse clinical manifestations. This review summarizes the genetic basis of these diseases, along with their clinical characteristics, diagnostic approaches, and disease-specific therapies.},
}

Humans
*Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy
*Motor Neuron Disease/genetics/diagnosis

@article {pmid40350140,
year = {2025},
author = {Amin, MA and Zehravi, M and Sweilam, SH and Shatu, MM and Durgawale, TP and Qureshi, MS and Durgapal, S and Haque, MA and Vodeti, R and Panigrahy, UP and Ahmad, I and Khan, S and Emran, TB},
title = {Neuroprotective potential of epigallocatechin gallate in Neurodegenerative Diseases: Insights into molecular mechanisms and clinical Relevance.},
journal = {Brain research},
volume = {},
number = {},
pages = {149693},
doi = {10.1016/j.brainres.2025.149693},
pmid = {40350140},
issn = {1872-6240},
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis pose significant challenges due to their complex pathophysiology and lack of effective treatments. Green tea, rich in the epigallocatechin gallate (EGCG) polyphenolic component, has demonstrated potential as a neuroprotective agent with numerous medicinal applications. EGCG effectively reduces tau and Aβ aggregation in ND models, promotes autophagy, and targets key signaling pathways like Nrf2-ARE, NF-κB, and MAPK. This review explores the molecular processes that underlie EGCG's neuroprotective properties, including its ability to regulate mitochondrial dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Clinical research indicates that EGCG may enhance cognitive and motor abilities, potentially inhibiting disease progression despite absorption and dose optimization limitations. The substance has been proven to slow the amyloidogenic process, prevent protein aggregation, decrease amyloid cytotoxicity, inhibit fibrillogenesis, and restructure fibrils for synergistic therapeutic effects. The review highlights the potential of EGCG as a natural, multi-targeted strategy for NDs but emphasizes the need for further clinical trials to enhance its therapeutic efficacy.},
}

@article {pmid40347374,
year = {2025},
author = {Varshney, V and Gabble, BC and Bishoyi, AK and Varma, P and Qahtan, SA and Kashyap, A and Panigrahi, R and Nathiya, D and Chauhan, AS},
title = {Exploring Exosome-Based Approaches for Early Diagnosis and Treatment of Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40347374},
issn = {1559-1182},
abstract = {Neurodegenerative diseases (NDs), like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), present an increasingly significant global health burden, primarily due to the lack of effective early diagnostic tools and treatments. Exosomes-nano-sized extracellular vesicles secreted by nearly all cell types-have emerged as promising candidates for both biomarkers and therapeutic agents in NDs. This review examines the biogenesis, molecular composition, and diverse functions of exosomes in NDs. Exosomes play a crucial role in mediating intercellular communication. They are capable of reflecting the biochemical state of their parent cells and have the ability to cross the blood-brain barrier (BBB). In doing so, they facilitate the propagation of pathological proteins, such as amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn), while also enabling the targeted delivery of neuroprotective compounds. Recent advancements in exosome isolation and engineering have opened up new possibilities for diagnostic and therapeutic strategies. These range from the discovery of non-invasive biomarkers to innovative approaches in gene therapy and drug delivery systems. However, challenges related to standardization, safety, and long-term effects must be addressed before exosomes can be translated into clinical applications. This review highlights both the promising potential and the obstacles that must be overcome to leverage exosomes in the treatment of NDs and the transformation of personalized medicine.},
}

@article {pmid40344943,
year = {2025},
author = {Zhou, ZD and Yi, L and Popławska-Domaszewicz, K and Chaudhuri, KR and Jankovic, J and Tan, EK},
title = {Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges.},
journal = {Pharmacological research},
volume = {216},
number = {},
pages = {107770},
doi = {10.1016/j.phrs.2025.107770},
pmid = {40344943},
issn = {1096-1186},
abstract = {Glucagon-like peptide-1 (GLP-1) receptor agonists (GRA) belong to a class of compounds that reduce blood glucose and energy intake by simulating actions of endogenous incretin hormone GLP-1 after it is released by the gut following food consumption. They are used to treat type 2 diabetes mellitus (T2DM) and obesity and have systemic effects on various organs, including the brain, liver, pancreas, heart, and the gut. Patients with T2DM have a higher risk of developing neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), accompanied by more severe motor deficits and faster disease progression, suggesting dysregulation of insulin signaling in these diseases. Experimental studies have shown that GRA have protective effects to modulate neuroinflammation, oxidative stress, mitochondrial and autophagic functions, and protein misfolding. Hence the compounds have generated enormous interest as novel therapeutic agents against NDs. To date, clinical trials have shown that three GRA, exenatide, liraglutide and lixisenatide can improve motor deficits as an add-on therapy in PD patients and liraglutide can improve cognitive function in AD patients. The neuroprotective effects of these and other GRA, such as PT320 (a sustained-released exenatide) and semaglutide, are still under investigation. The dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists have been demonstrated to have beneficial effects in AD and PD mice models. Overall, GRA are highly promising novel drugs, but future clinical studies should identify which subsets of patients should be targeted as potential candidates for their symptomatic and/or neuroprotective benefits, investigate whether combinations with other classes of drugs can further augment their efficacy, and evaluate their long-term disease-modifying and adverse effects.},
}

@article {pmid40340943,
year = {2025},
author = {Kellett, EA and Bademosi, AT and Walker, AK},
title = {Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {53},
pmid = {40340943},
issn = {1750-1326},
mesh = {Humans ; *DNA-Binding Proteins/metabolism ; Phosphorylation/physiology ; Animals ; *Neurodegenerative Diseases/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; },
abstract = {Increased phosphorylation of TDP-43 is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation and roles of TDP-43 phosphorylation remain incompletely understood. A variety of techniques have been utilized to understand TDP-43 phosphorylation, including kinase/phosphatase manipulation, phosphomimic variants, and genetic, physical, or chemical inducement in a variety of cell cultures and animal models, and via analyses of post-mortem human tissues. These studies have produced conflicting results: suggesting incongruously that TDP-43 phosphorylation may either drive disease progression or serve a neuroprotective role. In this review, we explore the roles of regulators of TDP-43 phosphorylation including the putative TDP-43 kinases c-Abl, CDC7, CK1, CK2, IKKβ, p38α/MAPK14, MEK1, TTBK1, and TTBK2, and TDP-43 phosphatases PP1, PP2A, and PP2B, in disease. Building on recent studies, we also examine the consequences of TDP-43 phosphorylation on TDP-43 pathology, especially related to TDP-43 mislocalisation, liquid-liquid phase separation, aggregation, and neurotoxicity. By comparing conflicting findings from various techniques and models, this review highlights both the discrepancies and unresolved aspects in the understanding of TDP-43 phosphorylation. We propose that the role of TDP-43 phosphorylation is site and context dependent, and includes regulation of liquid-liquid phase separation, subcellular mislocalisation, and degradation. We further suggest that greater consideration of the normal functions of the regulators of TDP-43 phosphorylation that may be perturbed in disease is warranted. This synthesis aims to build towards a comprehensive understanding of the complex role of TDP-43 phosphorylation in the pathogenesis of neurodegeneration.},
}

Humans
*DNA-Binding Proteins/metabolism
Phosphorylation/physiology
Animals
*Neurodegenerative Diseases/metabolism
Amyotrophic Lateral Sclerosis/metabolism

@article {pmid40340620,
year = {2025},
author = {Shen, D and Liu, A and Yang, X and Liu, Q and Liu, M and Cui, L},
title = {Exploring oculomotor challenges in amyotrophic lateral sclerosis: a comprehensive review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2025.2501690},
pmid = {40340620},
issn = {2167-9223},
abstract = {Traditionally understood as a motor neuron disease, amyotrophic lateral sclerosis (ALS) is now recognized to involve broader neurodegenerative processes, including the oculomotor system. This narrative review summarizes current evidence on oculomotor dysfunction in ALS, with a focus on its relationship to disease-related motor and cognitive impairments. Specifically, the review examines key eye-tracking (ET) metrics, including saccades, smooth pursuit, and fixation, highlighting their potential to reflect both motor and extramotor degeneration. Notably, patients with bulbar-onset ALS exhibit more pronounced oculomotor impairments. By synthesizing findings on the connection between oculomotor dysfunction and cognitive decline, this review underscores the potential of ET as a noninvasive tool for assessing ALS progression. Oculomotor metrics, as part of a broader understanding of ALS's impact on multiple neural networks, may offer valuable insights to refine patient assessment and care strategies, particularly in advanced disease stages.},
}

@article {pmid40333317,
year = {2025},
author = {Simula, ER and Jasemi, S and Cossu, D and Fais, M and Cossu, I and Chessa, V and Canu, M and Sechi, LA},
title = {Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.},
journal = {Vaccines},
volume = {13},
number = {4},
pages = {},
pmid = {40333317},
issn = {2076-393X},
support = {PNRR-MCNT1-2023-12376993//Ministero della Salute/ ; 2022BP837R//MUR, PRIN 2022/ ; 22//Regione Autonoma Sardegna grant: legge regionale 12 22 December 2022/ ; e.INS Ecosystem of Innovation for Next Generation Sardinia spoke n 5//European Union/ ; },
abstract = {Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs' biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions.},
}

@article {pmid40332510,
year = {2025},
author = {Stacchiotti, C and Mazzella di Regnella, S and Cinotti, M and Spalloni, A and Volpe, E},
title = {Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332510},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology ; *Cytokines/therapeutic use/metabolism ; Animals ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/metabolism ; Inflammation ; },
abstract = {Neuroinflammation is an inflammatory response occurring within the central nervous system (CNS). The process is marked by the production of pro-inflammatory cytokines, chemokines, small-molecule messengers, and reactive oxygen species. Microglia and astrocytes are primarily involved in this process, while endothelial cells and infiltrating blood cells contribute to neuroinflammation when the blood-brain barrier (BBB) is damaged. Neuroinflammation is increasingly recognized as a pathological hallmark of several neurological diseases, including amyotrophic lateral sclerosis (ALS), and is closely linked to neurodegeneration, another key feature of ALS. In fact, neurodegeneration is a pathological trigger for inflammation, and neuroinflammation, in turn, contributes to motor neuron (MN) degeneration through the induction of synaptic dysfunction, neuronal death, and inhibition of neurogenesis. Importantly, resolution of acute inflammation is crucial for avoiding chronic inflammation and tissue destruction. Inflammatory processes are mediated by soluble factors known as cytokines, which are involved in both promoting and inhibiting inflammation. Cytokines with anti-inflammatory properties may exert protective roles in neuroinflammatory diseases, including ALS. In particular, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-4, IL-13, and IL-9 have been shown to exert an anti-inflammatory role in the CNS. Other recently emerging immune regulatory cytokines in the CNS include IL-35, IL-25, IL-37, and IL-27. This review describes the current understanding of neuroinflammation in ALS and highlights recent advances in the role of anti-inflammatory cytokines within CNS with a particular focus on their potential therapeutic applications in ALS. Furthermore, we discuss current therapeutic strategies aimed at enhancing the anti-inflammatory response to modulate neuroinflammation in this disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology
*Cytokines/therapeutic use/metabolism
Animals
*Neuroinflammatory Diseases/drug therapy/metabolism/pathology
*Anti-Inflammatory Agents/therapeutic use/pharmacology
Blood-Brain Barrier/metabolism
Inflammation

@article {pmid40280464,
year = {2025},
author = {Gritsiuta, AI and Reep, G and Parupudi, S and Petrov, RV},
title = {Optimizing the management of anastomotic leaks after esophagectomy: a narrative review of salvage strategies and outcomes.},
journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract},
volume = {29},
number = {7},
pages = {102069},
doi = {10.1016/j.gassur.2025.102069},
pmid = {40280464},
issn = {1873-4626},
abstract = {BACKGROUND: Anastomotic leaks (ALs) after esophagectomy remain a major postoperative complication, leading to increased morbidity, prolonged hospital stays, and higher mortality. Despite advancements in surgical techniques and perioperative care, AL management lacks standardized protocols. This review aimed to evaluate current salvage strategies, including conservative, endoscopic, and surgical approaches, to optimize outcomes and reduce complications.

METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar databases to identify studies published between 2000 and 2025 on AL management after esophagectomy. Peer-reviewed clinical trials, guidelines, and expert consensus reports were reviewed, focusing on minimally invasive and surgical interventions, patient outcomes, and emerging treatment strategies.

RESULTS: AL management strategies were classified into 3 primary approaches. Conservative management includes nutritional support, antibiotic therapy, and percutaneous drainage, particularly for contained leaks. Endoscopic interventions, such as self-expanding metal stents and endoscopic vacuum-assisted closure, have shown high success rates, with vacuum-assisted closure achieving superior closure outcomes. Hybrid techniques, including stent-over-sponge and vacuum-assisted closure-stent, are emerging as promising alternatives. Surgical interventions remain the gold standard for severe or refractory leaks with options, including primary repair, esophageal diversion, and delayed conduit reconstruction.

CONCLUSION: A multidisciplinary approach is crucial for optimizing AL management, incorporating enhanced recovery protocols, early risk assessment, and individualized treatment plans. Endoscopic techniques have reduced the need for surgical revisions, but surgical intervention remains necessary for severe cases. Future research should focus on refining treatment algorithms, integrating novel technologies, and establishing standardized guidelines to improve patient survival and quality of life.},
}

@article {pmid40332015,
year = {2025},
author = {Duță, C and Dogaru, CB and Muscurel, C and Stoian, I},
title = {Nanozymes: Innovative Therapeutics in the Battle Against Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
doi = {10.3390/ijms26083522},
pmid = {40332015},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/chemistry/pharmacology ; *Nanostructures/chemistry/therapeutic use ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), represent a significant challenge to global health due to their progressive nature and the absence of curative treatments. These disorders are characterized by oxidative stress, protein misfolding, and neuroinflammation, which collectively contribute to neuronal damage and death. Recent advancements in nanotechnology have introduced nanozymes-engineered nanomaterials that mimic enzyme-like activities-as promising therapeutic agents. This review explores the multifaceted roles of nanozymes in combating oxidative stress and inflammation in neurodegenerative conditions. By harnessing their potent antioxidant properties, nanozymes can effectively scavenge reactive oxygen species (ROS) and restore redox balance, thereby protecting neuronal function. Their ability to modify surface properties enhances targeted delivery and biocompatibility, making them suitable for various biomedical applications. In this review, we highlight recent findings on the design, functionality, and therapeutic potential of nanozymes, emphasizing their dual role in addressing oxidative stress and pathological features such as protein aggregation. This synthesis of current research underscores the innovative potential of nanozymes as a proactive therapeutic strategy to halt disease progression and improve patient outcomes in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
Oxidative Stress/drug effects
Animals
Antioxidants/therapeutic use/chemistry/pharmacology
*Nanostructures/chemistry/therapeutic use
Reactive Oxygen Species/metabolism

@article {pmid40328798,
year = {2025},
author = {Wu, X and Yang, Z and Zou, J and Gao, H and Shao, Z and Li, C and Lei, P},
title = {Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.},
journal = {Signal transduction and targeted therapy},
volume = {10},
number = {1},
pages = {146},
pmid = {40328798},
issn = {2059-3635},
support = {32070961//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology ; *Drug Discovery ; *Protein Kinases/genetics/metabolism ; *Protein Kinase Inhibitors/therapeutic use ; Signal Transduction/drug effects/genetics ; Phosphorylation ; Animals ; },
abstract = {Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's disease, and Amyotrophic Lateral Sclerosis) are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy. Although progress has been made, there is still a lack of effective cures to date, and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development. Protein phosphorylation, regulated by protein kinases and protein phosphatases, participates in most cellular events, whereas aberrant phosphorylation manifests as a main cause of diseases. As evidenced by pharmacological and pathological studies, protein kinases are proven to be promising therapeutic targets for various diseases, such as cancers, central nervous system disorders, and cardiovascular diseases. The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed, but a systematic summary of the role of protein kinases in the nervous system is lacking. Here, we focus on the involvement of protein kinases in neurodegenerative diseases, by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases. We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases, illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies (such as antisense oligonucleotides and gene therapy) for effective prevention and early intervention.},
}

Humans
*Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology
*Drug Discovery
*Protein Kinases/genetics/metabolism
*Protein Kinase Inhibitors/therapeutic use
Signal Transduction/drug effects/genetics
Phosphorylation
Animals

@article {pmid40328546,
year = {2025},
author = {Kleinerova, J and Tan, EL and Delaney, S and Smyth, M and Bede, P},
title = {Advances and research priorities in the respiratory management of ALS: Historical perspectives and new technologies.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2025.04.008},
pmid = {40328546},
issn = {0035-3787},
abstract = {Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been undertaken to clarify the pathophysiology and progression rates associated with respiratory compromise and effective management strategies have been developed. Clinical trials routinely incorporate respiratory measures as study end points, non-invasive ventilation is now widely used in the home setting, cough-assist techniques are commonly used, advanced neurophysiology techniques and wearable technologies have been integrated into respiratory monitoring protocols, and palliative guidelines have been developed to effectively manage respiratory distress. Despite the widespread implementation of these interventions, epidemiology studies are inconsistent and some studies suggest that survival in ALS has not improved significantly with the introduction of these measures. The outcomes of diaphragmatic pacing trials have been disappointing, advanced neurophysiology techniques are not routinely utilised, spinal and brainstem imaging are not commonly undertaken and significant geographical differences exist in proceeding to tracheostomy. The worldwide COVID pandemic has given impetus for remote monitoring, connected devices, video-consultations, and timely vaccinations in ALS; lessons that are invaluable long after the pandemic. Respiratory monitoring and management in ALS is a swiftly evolving facet of ALS care with considerable quality of life benefits.},
}

@article {pmid40325332,
year = {2025},
author = {Liu, S and Feng, A and Li, Z},
title = {Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40325332},
issn = {1559-1182},
abstract = {The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.},
}

@article {pmid40022581,
year = {2025},
author = {Galvin, M and Heverin, M and Mac Domhnaill, É and Mcfarlane, R and Meldrum, D and Murray, D and Bolger, A and Connelly, J and Flynn, K and Fox, E and Gibbons, F and Hederman, L and Impey, S and O'Keefe, I and O'Meara, C and McKibben, D and Nicholson, M and Stephens, G and Van Dijk, J and Van Den Berg, L and Hardiman, O},
title = {Challenges and solutions to complex data governance issues in cross-national, cross-sectoral, multidisciplinary real world health research: a descriptive overview.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {sup1},
pages = {1-7},
doi = {10.1080/21678421.2024.2428927},
pmid = {40022581},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/epidemiology ; *Biomedical Research ; *Precision Medicine ; Europe ; *Data Management ; },
abstract = {Real-world clinical data is generated during clinical engagements. The collection and further processing and mining of clinical information requires consents and navigation of necessary and important data governance processes. PRECISION ALS is an academic industry programme that collects, collates and analyses clinical and para-clinical data from patients with ALS across 10 European sites. The infrastructure of PRECISION ALS represents a complex interplay of the clinical, governance, and technical frameworks. Incorporation of infrastructural and operational measures enables sophisticated cross-national, cross-sectoral and cross disciplinary health research. PRECISION ALS has established a range of domain expertise, technologies, governance and clinical data management practices that can be applied throughout the life cycle of patient data from generation, collation, delivery and secure storage for advanced analytics. PRECISION ALS is designed to move the field of ALS research to a true Precision Medicine based approach toward new and more effective therapeutics.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/epidemiology
*Biomedical Research
*Precision Medicine
Europe
*Data Management

@article {pmid39440770,
year = {2025},
author = {Allowitz, K and Taylor, J and Harames, K and Yoo, J and Baloch, O and Ramana, KV},
title = {Oxidative Stress-mediated Lipid Peroxidation-derived Lipid Aldehydes in the Pathophysiology of Neurodegenerative Diseases.},
journal = {Current neuropharmacology},
volume = {23},
number = {6},
pages = {671-685},
pmid = {39440770},
issn = {1875-6190},
mesh = {Humans ; *Oxidative Stress/physiology ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Lipid Peroxidation/physiology ; *Aldehydes/metabolism ; Animals ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis cause damage and gradual loss of neurons affecting the central nervous system. Neurodegenerative diseases are most commonly seen in the ageing process. Ageing causes increased reactive oxygen species and decreased mitochondrial ATP generation, resulting in redox imbalance and oxidative stress. Oxidative stress-generated free radicals cause damage to membrane lipids containing polyunsaturated fatty acids, leading to the formation of toxic lipid aldehyde products such as 4- hydroxynonenal and malondialdehyde. Several studies have shown that lipid peroxidation-derived aldehyde products form adducts with cellular proteins, altering their structure and function. Thus, these lipid aldehydes could act as secondary signaling intermediates, modifying important metabolic pathways, and contributing to the pathophysiology of several human diseases, including neurodegenerative disorders. Additionally, they could serve as biomarkers for disease progression. This narrative review article discusses the biological and clinical significance of oxidative stress-mediated lipid peroxidation-derived lipid aldehydes in the pathophysiology of various neurodegenerative diseases.},
}

Humans
*Oxidative Stress/physiology
*Neurodegenerative Diseases/metabolism/physiopathology
*Lipid Peroxidation/physiology
*Aldehydes/metabolism
Animals

@article {pmid40320859,
year = {2025},
author = {Watanabe, S and Yamanaka, K},
title = {Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e70016},
doi = {10.1002/bies.70016},
pmid = {40320859},
issn = {1521-1878},
support = {23K06826//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 19KK0214//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 22H00467//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; JP22ek0109426//Japan Agency for Medical Research and Development/ ; JP24wm0425014//Japan Agency for Medical Research and Development/ ; JP24wm0625301//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; //Mochida Memorial Foundation for Medical and Pharmaceutical Research/ ; //Kowa Life Science Foundation/ ; //Novartis Foundation/ ; },
abstract = {Recent evidence indicates that the mitochondria-endoplasmic reticulum (ER) contact site is a novel microdomain essential for cellular homeostasis. Various proteins are accumulated at the mitochondria-associated membrane (MAM), an ER subcomponent closely associated with the mitochondria, contributing to Ca[2+] transfer to the mitochondria, lipid synthesis, mitochondrial fission/fusion, and autophagy. These functions are disrupted in the diseases, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In this review, we summarize the disruption of protein homeostasis in various neurodegenerative diseases, present recent works on the mechanisms of MAM aberration, including ours mainly focused on ALS, and then discuss challenges and prospects for future MAM-targeted therapies in neurodegenerative diseases.},
}

@article {pmid40320052,
year = {2025},
author = {Nadeem, A and Sharma, P and Gupta, P and Sandeep, P and Sharma, B and Sharma, N and Yadav, M and Dhiman, N},
title = {Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {116964},
doi = {10.1016/j.bcp.2025.116964},
pmid = {40320052},
issn = {1873-2968},
abstract = {Neuregulin 3 (NRG3) is an epidermal growth factor related protein that binds to and stimulates the Erb-B2 receptor tyrosine kinase 4 (ErbB4). NRG3 is a multifunctional protein with fifteen alternative splicing isoforms categorized into four classes. Numerous physiological processes, such as the formation of cortical plate, cortical patterning, synaptic development, neuronal proliferation, regulation of neurotransmission, control of impulsive behavior, mammary gland morphogenesis, spermatogonial proliferation and cardiac homeostasis are influenced by NRG3. Besides its physiological roles, NRG3 also modulates anxiogenic phenotypes. It is a susceptibility gene for schizophrenia, autism spectrum disorder and Hirschsprung's Disease. Furthermore, anxiety during nicotine withdrawal is dependent on NRG3-ErbB4 signaling. Research on a range of solid carcinomas, such as brain tumors, ovarian cancer, gastrointestinal cancer and breast cancer, has demonstrated NRG3 gene as a therapeutic target. NRG3 also has potential involvement in epilepsy, angular limb malformation in Rambouillet rams, amyotrophic lateral sclerosis and polythelia. Nevertheless, little is known about the molecular characteristics, activities specific to isoforms, and molecular mechanisms of NRG3. Examining its potential involvement in a range of physiological processes and pathological states is a unique area that needs in-depth study and may offer new mechanistic insights and comprehension of these elements. Thus, the purpose of this review is to shed light on the utility of NRG3 as a potential target in various health and disease conditions.},
}

@article {pmid40319325,
year = {2025},
author = {Mehdizadeh, S and Mamaghani, M and Hassanikia, S and Pilehvar, Y and Ertas, YN},
title = {Exosome-powered neuropharmaceutics: unlocking the blood-brain barrier for next-gen therapies.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {329},
pmid = {40319325},
issn = {1477-3155},
mesh = {*Exosomes/metabolism/chemistry ; *Blood-Brain Barrier/metabolism/drug effects ; Humans ; Animals ; *Drug Delivery Systems/methods ; *Neuropharmacology/methods ; Drug Carriers/chemistry ; },
abstract = {BACKGROUND: The blood-brain barrier (BBB) presents a formidable challenge in neuropharmacology, limiting the delivery of therapeutic agents to the brain. Exosomes, nature's nanocarriers, have emerged as a promising solution due to their biocompatibility, low immunogenicity, and innate ability to traverse the BBB. A thorough examination of BBB anatomy and physiology reveals the complexities of neurological drug delivery and underscores the limitations of conventional methods.

MAIN BODY: This review explores the potential of exosome-powered neuropharmaceutics, highlighting their structural and functional properties, biogenesis, and mechanisms of release. Their intrinsic advantages in drug delivery, including enhanced stability and efficient cellular uptake, are discussed in detail. Exosomes naturally overcome BBB barriers through specific translocation mechanisms, making them a compelling vehicle for targeted brain therapies. Advances in engineering strategies, such as genetic and biochemical modifications, drug loading techniques, and specificity enhancement, further bolster their therapeutic potential. Exosome-based approaches hold immense promise for treating a spectrum of neurological disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), brain tumors, stroke, and psychiatric conditions.

CONCLUSION: By leveraging their innate properties and engineering innovations, exosomes offer a versatile platform for precision neurotherapeutics. Despite their promise, challenges remain in clinical translation, including large-scale production, standardization, and regulatory considerations. Future research directions in exosome nanobiotechnology aim to refine these therapeutic strategies, unlocking new avenues for treating neurological diseases. This review underscores the transformative impact of exosome-based drug delivery, paving the way for next-generation therapies that can effectively penetrate the BBB and revolutionize neuropharmacology.},
}

*Exosomes/metabolism/chemistry
*Blood-Brain Barrier/metabolism/drug effects
Humans
Animals
*Drug Delivery Systems/methods
*Neuropharmacology/methods
Drug Carriers/chemistry

@article {pmid40314791,
year = {2025},
author = {Iuzzolino, VV and Scaravilli, A and Carignani, G and Senerchia, G and Pontillo, G and Dubbioso, R and Cocozza, S},
title = {Mapping motor and extra-motor gray and white matter changes in ALS: a comprehensive review of MRI insights.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {40314791},
issn = {1432-1920},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, yet with substantial clinical variability. Furthermore, beyond motor symptoms, ALS patients also show non-motor features, reflecting its classification as a multi-system disorder. The identification of reliable biomarkers is a critical challenge for improving diagnosis, tracking disease progression, and predicting patient outcomes. This review explores macro- and microstructural alterations in ALS, focusing on gray matter (GM) and white matter (WM) as observed through Magnetic Resonance Imaging (MRI). This approach synthesizes not only the expected involvement of motor areas but also highlights emerging evidence that these changes extend to extra-motor areas, such as the frontal and temporal lobes, underscoring the complex pathophysiology of ALS. The review emphasizes the potential of MRI as a non-invasive tool to provide new biomarkers by assessing both GM and WM integrity, a key advancement in ALS research. Additionally, it addresses existing discrepancies in findings and stresses the need for standardized imaging protocols. It also highlights the role of multi-modal MRI approaches in deepening our understanding of ALS pathology, emphasizing the importance of combining structural and diffusion MRI techniques to offer more comprehensive insights into ALS progression, ultimately advancing the potential for personalized treatment strategies and improving patient outcomes.},
}

@article {pmid40309800,
year = {2025},
author = {Manai, AL and Caria, P and Noli, B and Contini, C and Manconi, B and Etzi, F and Cocco, C},
title = {VGF and Its Derived Peptides in Amyotrophic Lateral Sclerosis.},
journal = {Brain sciences},
volume = {15},
number = {4},
pages = {},
pmid = {40309800},
issn = {2076-3425},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration in the neurons of the frontal cortex, spinal cord, and brainstem, altering the correct release of neurotransmitters. The disease affects every muscle in the body and could cause death three to five years after symptoms first occur. There is currently no efficient treatment to stop the disease's progression. The lack of identification of potential therapeutic strategies is a consequence of the delayed diagnosis due to the absence of accurate ALS early biomarkers. Indeed, neurotransmitters altered in ALS are not measurable in body fluids at quantities that allow for testing, making their use as diagnostic tools a challenge. Contrarily, neuroproteins and neuropeptides are chemical messengers produced and released by neurons, and most of them have the potential to enter bodily fluids. To find out new possible ALS biomarkers, the research of neuropeptides and proteins is intensified using mass spectrometry and biochemical-based assays. Neuropeptides derived from the proVGF precursor protein act as signaling molecules within neurons. ProVGF and its derived peptides are expressed in the nervous and endocrine systems but are also widely distributed in body fluids such as blood, urine, and cerebrospinal fluid, making them viable options as disease biomarkers. To highlight the proVGF and its derived peptides' major roles as ALS diagnostic biomarkers, this review provides an overview of the VGF peptide alterations in spinal cord and body fluids and outlines the limitations of the reported investigations.},
}

@article {pmid40309789,
year = {2025},
author = {Khan, S and Kallis, L and Mee, H and El Hadwe, S and Barone, D and Hutchinson, P and Kolias, A},
title = {Invasive Brain-Computer Interface for Communication: A Scoping Review.},
journal = {Brain sciences},
volume = {15},
number = {4},
pages = {},
pmid = {40309789},
issn = {2076-3425},
abstract = {BACKGROUND: The rapid expansion of the brain-computer interface for patients with neurological deficits has garnered significant interest, and for patients, it provides an additional route where conventional rehabilitation has its limits. This has particularly been the case for patients who lose the ability to communicate. Circumventing neural injuries by recording from the intact cortex and subcortex has the potential to allow patients to communicate and restore self-expression. Discoveries over the last 10-15 years have been possible through advancements in technology, neuroscience, and computing. By examining studies involving intracranial brain-computer interfaces that aim to restore communication, we aimed to explore the advances made and explore where the technology is heading.

METHODS: For this scoping review, we systematically searched PubMed and OVID Embase. After processing the articles, the search yielded 41 articles that we included in this review.

RESULTS: The articles predominantly assessed patients who had either suffered from amyotrophic lateral sclerosis, cervical cord injury, or brainstem stroke, resulting in tetraplegia and, in some cases, difficulty speaking. Of the intracranial implants, ten had ALS, six had brainstem stroke, and thirteen had a spinal cord injury. Stereoelectroencephalography was also used, but the results, whilst promising, are still in their infancy. Studies involving patients who were moving cursors on a screen could improve the speed of movement by optimising the interface and utilising better decoding methods. In recent years, intracortical devices have been successfully used for accurate speech-to-text and speech-to-audio decoding in patients who are unable to speak.

CONCLUSIONS: Here, we summarise the progress made by BCIs used for communication. Speech decoding directly from the cortex can provide a novel therapeutic method to restore full, embodied communication to patients suffering from tetraplegia who otherwise cannot communicate.},
}

@article {pmid40309514,
year = {2025},
author = {Li, V and Huang, Y},
title = {Oligonucleotide therapeutics for neurodegenerative diseases.},
journal = {NeuroImmune pharmacology and therapeutics},
volume = {4},
number = {1},
pages = {1-11},
pmid = {40309514},
issn = {2750-6665},
abstract = {Recently there has been a surge in interest involving the application of oligonucleotides, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), for the treatment of chronic diseases that have few available therapeutic options. This emerging class of drugs primarily operates by selectively suppressing target genes through antisense and/or RNA interference mechanisms. While various commercial medications exist for delivering oligonucleotides to the hepatic tissue, achieving effective delivery to extra hepatic tissues remains a formidable challenge. Here, we review recent advances in oligonucleotide technologies, including nanoparticle delivery, local administration, and 2'-O-hexadecyl (C16)-conjugation that work to extend the applicability of siRNAs and ASOs to nerve tissues. We discuss critical factors pivotal for the successful clinical translations of these modified or engineered oligonucleotides in the context of treating neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis.},
}

@article {pmid40305176,
year = {2025},
author = {Erichsen, PA and Henriksen, EE and Nielsen, JE and Ejlerskov, P and Simonsen, AH and Toft, A},
title = {Immunological Fluid Biomarkers in Frontotemporal Dementia: A Systematic Review.},
journal = {Biomolecules},
volume = {15},
number = {4},
pages = {},
pmid = {40305176},
issn = {2218-273X},
support = {0084960//Novo Nordisk Foundation/ ; R450-2023-989//Lundbeck Foundation/ ; },
mesh = {Humans ; *Frontotemporal Dementia/immunology/blood/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid/blood ; Alzheimer Disease/immunology/blood/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood ; Chemokine CCL2/cerebrospinal fluid/blood ; },
abstract = {Dysregulated immune activation plays a key role in the pathogenesis of neurodegenerative diseases, including frontotemporal dementia (FTD). This study reviews immunological biomarkers associated with FTD and its subtypes. A systematic search of PubMed and Web of Science was conducted for studies published before 1 January 2025, focusing on immunological biomarkers in CSF or blood from FTD patients with comparisons to healthy or neurological controls. A total of 124 studies were included, involving 6686 FTD patients and 202 immune biomarkers. Key findings include elevated levels of GFAP and MCP1/CCL2 in both CSF and blood and consistently increased CHIT1 and YKL-40 in CSF. Complement proteins from the classical activation pathway emerged as promising targets. Distinct immune markers were found to differentiate FTD from Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), with GFAP, SPARC, and SPP1 varying between FTD and AD and IL-15, HERV-K, NOD2, and CHIT1 differing between FTD and ALS. A few markers, such as Galectin-3 and PGRN, distinguished FTD subtypes. Enrichment analysis highlighted IL-10 signaling and immune cell chemotaxis as potential pathways for further exploration. This study provides an overview of immunological biomarkers in FTD, emphasizing those most relevant for future research on immune dysregulation in FTD pathogenesis.},
}

Humans
*Frontotemporal Dementia/immunology/blood/cerebrospinal fluid
*Biomarkers/cerebrospinal fluid/blood
Alzheimer Disease/immunology/blood/cerebrospinal fluid
Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid
Chitinase-3-Like Protein 1/cerebrospinal fluid/blood
Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood
Chemokine CCL2/cerebrospinal fluid/blood

@article {pmid40302786,
year = {2025},
author = {Vijayaraghavan, M and Murali, SP and Thakur, G and Li, XJ},
title = {Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1553658},
pmid = {40302786},
issn = {1662-5102},
abstract = {This review provides a comprehensive overview of hereditary spastic paraplegias (HSPs) and summarizes the recent progress on the role of glial cells in the pathogenesis of HSPs. HSPs are a heterogeneous group of neurogenetic diseases characterized by axonal degeneration of cortical motor neurons, leading to muscle weakness and atrophy. Though the contribution of glial cells, especially astrocytes, to the progression of other motor neuron diseases like amyotrophic lateral sclerosis (ALS) is well documented, the role of glial cells and the interaction between neurons and astrocytes in HSP remained unknown until recently. Using human pluripotent stem cell-based models of HSPs, a study reported impaired lipid metabolisms and reduced size of lipid droplets in HSP astrocytes. Moreover, targeting lipid dysfunction in astrocytes rescues axonal degeneration of HSP cortical neurons, demonstrating a non-cell-autonomous mechanism in axonal deficits of HSP neurons. In addition to astrocytes, recent studies revealed dysfunctions in HSP patient pluripotent stem cell-derived microglial cells. Increased microgliosis and pro-inflammation factors were also observed in HSP patients' samples, pointing to an exciting role of innate immunity and microglia in HSP. Building upon these recent studies, further investigation of the detailed molecular mechanism and the interplay between glial cell dysfunction and neuronal degeneration in HSP by combining human stem cell models, animal models, and patient samples will open avenues for identifying new therapeutic targets and strategies for HSP.},
}

@article {pmid40301152,
year = {2025},
author = {Armas, JMB and Taoro-González, L and Fisher, EMC and Acevedo-Arozena, A},
title = {Challenges of modelling TDP-43 pathology in mice.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {},
number = {},
pages = {},
pmid = {40301152},
issn = {1432-1777},
abstract = {TDP-43 is a normally nuclear RNA binding protein that under pathological conditions may be excluded from the nucleus and deposited in the cytoplasm in the form of insoluble polyubiquitinated and polyphosphorylated inclusions. This nuclear exclusion coupled with cytoplasmic accumulation is called TDP-43 pathology and contributes to a range of disorders collectively known as TDP-43 proteinopathies. These include the great majority of amyotrophic lateral sclerosis (ALS) cases, all limbic-predominant age-related TDP-43 encephalopathy (LATE), as well as up to 50% of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) cases. Thus, TDP-43 pathology is a common feature underlying a wide range of neurodegenerative conditions. However, modelling it has proven to be challenging, particularly generating models with concomitant TDP-43 loss of nuclear function and cytoplasmic inclusions. Here, focussing exclusively on mice, we discuss TDP-43 genetic models in terms of the presence of TDP-43 pathology, and we consider other models with TDP-43 pathology due to mutations in disparate genes. We also consider manipulations aimed at producing TDP-43 pathology, and we look at potential strategies to develop new, much needed models to address the many outstanding questions regarding how and why TDP-43 protein leaves the nucleus and accumulates in the cytoplasm, causing downstream dysfunction and devastating disease.},
}

@article {pmid39779313,
year = {2025},
author = {Xiao, Y and Tan, Y and Li, C and Wei, Q and Jiang, Q and Wang, S and Yang, T and Lin, J and Zhang, L and Shang, H},
title = {Genetic and clinical analysis of OPTN in amyotrophic lateral sclerosis.},
journal = {Journal of medical genetics},
volume = {62},
number = {4},
pages = {242-248},
doi = {10.1136/jmg-2024-109978},
pmid = {39779313},
issn = {1468-6244},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Membrane Transport Proteins/genetics ; *Cell Cycle Proteins/genetics ; *Transcription Factor TFIIIA/genetics ; Female ; Male ; Middle Aged ; Genetic Association Studies ; Phenotype ; Genotype ; *Genetic Predisposition to Disease ; Aged ; Adult ; Mutation ; Asian People/genetics ; },
abstract = {BACKGROUND: Considerable heterogeneity in genotypes and phenotypes has been observed among patients with amyotrophic lateral sclerosis (ALS) harbouring optineurin gene (OPTN) mutations, as reported in prior studies. The study aimed to elucidate the correlation between OPTN genotypes and phenotypes.

METHODS: OPTN gene variants were screened within a substantial Chinese cohort of patients with ALS, encompassing LoF and rare missense variants. Additionally, a systematic literature review was conducted to compile the spectrum of OPTN mutations and explore the relationship between the genotype and phenotype of patients with ALS with OPTN.

RESULTS: A total of 33 unrelated patients with ALS with 24 rare OPTN variants, including 17 novel variants, were identified in 2279 patients with ALS. Among 24 variants in our cohort and 106 variants in previous studies, only 33.3% and 35.8% were pathogenic/likely pathogenic variants. Moreover, the frequency of OPTN variants in the Asian ALS population was higher (1.08%) than that of the Caucasian population (0.55%). For the phenotype of patients with ALS carrying OPTN variants, we found that patients with pathogenic/likely pathogenic variants had the highest baseline progression rate and the shortest survival time among groups in our cohort.

CONCLUSION: Our study contributed to a broader understanding of the genotype and phenotype spectrum of patients with ALS carrying OPTN variants. Further investigations are warranted to definitively establish the genotype-phenotype associations.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Membrane Transport Proteins/genetics
*Cell Cycle Proteins/genetics
*Transcription Factor TFIIIA/genetics
Female
Male
Middle Aged
Genetic Association Studies
Phenotype
Genotype
*Genetic Predisposition to Disease
Aged
Adult
Mutation
Asian People/genetics

@article {pmid40300682,
year = {2025},
author = {Li, Z and Xing, J},
title = {Role of sirtuins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic potential.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {143591},
doi = {10.1016/j.ijbiomac.2025.143591},
pmid = {40300682},
issn = {1879-0003},
abstract = {The high incidence and mortality rate of cardiac arrest (CA) establishes it as a critical clinical challenge in emergency medicine globally. Despite continuous advances in advanced life support (ALS) technology, the prognosis for patients experiencing cardiac arrest remains poor, with cerebral ischemia and reperfusion injury (CIRI) being a significant determinant of adverse neurological outcomes and increased mortality. Sirtuins (SIRTs) are a class of highly evolutionarily conserved NAD[+]-dependent histone deacylenzymes capable of regulating the expression of various cytoprotective genes to play a neuroprotective role in CIRI. SIRTs mainly regulate the levels of downstream proteins such as PGC 1-α, Nrf 2, NLRP 3, FoxOs, and PINK 1 to inhibit inflammatory response, attenuate oxidative stress, improve mitochondrial dysfunction, promote angiogenesis, and inhibit apoptosis while reducing CIRI. Natural active ingredients are widely used in regulating the protein level of SIRTs in the body because of their multi-components, multi-pathway, multi-target, and minimal toxic side effects. However, these naturally active ingredients still face many challenges related to drug targeting, pharmacokinetic properties, and drug delivery. The emergence and vigorous development of new drug delivery systems, such as nanoparticles, micromilk, and exosomes, provide strong support for solving the above problems. In the context of the rapid development of molecular biology technology, non-coding RNA (NcRNA), represented by miRNA and LncRNA, offers great potential for achieving gene-level precision medicine. In the context of multidisciplinary integration, combining SIRTs proteins with biotechnology, omics technologies, artificial intelligence, and material science will strongly promote the deepening of their basic research and expand their clinical application. This review describes the major signaling pathways of targeting SIRTs to mitigate CIRI, as well as the current research status of Chinese and Western medicine and medical means for the intervention level of SIRTs. Meanwhile, the challenges and possible solutions in the clinical application of targeted drugs are summarized. In the context of medical and industrial crossover, the development direction of SIRTs in the future is discussed to provide valuable reference for basic medical researchers and clinicians to improve the clinical diagnosis and treatment effects of CIRI.},
}

@article {pmid40300213,
year = {2025},
author = {Sun, Y and Vermulst, M},
title = {The hidden costs of imperfection: transcription errors in protein aggregation diseases.},
journal = {Current opinion in genetics & development},
volume = {93},
number = {},
pages = {102350},
doi = {10.1016/j.gde.2025.102350},
pmid = {40300213},
issn = {1879-0380},
abstract = {At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer's and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.},
}

@article {pmid40299664,
year = {2025},
author = {Nogueira-Machado, JA and Rocha-Silva, F and Gomes, NA},
title = {The Role of mTOR in Amyotrophic Lateral Sclerosis.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
doi = {10.3390/biomedicines13040952},
pmid = {40299664},
issn = {2227-9059},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS.},
}

@article {pmid40299512,
year = {2025},
author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R},
title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
doi = {10.3390/biomedicines13040915},
pmid = {40299512},
issn = {2227-9059},
abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.},
}

@article {pmid40299102,
year = {2025},
author = {Zhang, G and Huang, S and Wei, M and Wu, Y and Wang, J},
title = {Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.},
journal = {Neurochemical research},
volume = {50},
number = {3},
pages = {155},
pmid = {40299102},
issn = {1573-6903},
support = {2023JJB140089//Guangxi Youth Science Foundation Project/ ; 82201694//the National Natural Scientific Foundation of China/ ; 2022AC21033//Guangxi Science and technology base and talent project/ ; 2022KY0349//Guangxi university young and middle-aged teachers' basic ability improvement project/ ; },
mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Glutamate Plasma Membrane Transport Proteins/metabolism ; Glutamic Acid/metabolism ; },
abstract = {Excitatory amino acid transporters (EAATs) are pivotal regulators of glutamate homeostasis in the central nervous system and orchestrate synaptic glutamate clearance through transmembrane transport and the glutamine‒glutamate cycle. The five EAAT subtypes (GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, and EAAT5) exhibit spatiotemporal-specific expression patterns in neurons and glial cells, and their dysfunction is implicated in diverse neurological pathologies, including epilepsy, amyotrophic lateral sclerosis (ALS), schizophrenia, depression, and retinal degeneration. Mechanistic studies revealed that astrocytic GLT-1 deficiency disrupts glutamate clearance in ALS motor neurons, whereas GLAST genetic variants are linked to both epilepsy susceptibility and glaucomatous retinal ganglion cell degeneration. Three major challenges persist in ongoing research: ① subtype-specific regulatory mechanisms remain unclear; ② compensatory functions of transporters vary significantly across disease models; and ③ clinical translation lacks standardized evaluation criteria. The interaction mechanisms and dynamic roles of EAATs in neurological disorders were systematically investigated in this study, and an integrated approach combining single-cell profiling, stem cell-based disease modeling, and drug screening platforms was proposed. These findings lay the groundwork for novel therapeutic strategies targeting glutamate homeostasis.},
}

Humans
Animals
*Nervous System Diseases/metabolism/drug therapy
*Glutamate Plasma Membrane Transport Proteins/metabolism
Glutamic Acid/metabolism

@article {pmid40299101,
year = {2025},
author = {Sarkar, S and Porel, P and Kosey, S and Aran, KR},
title = {Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {436},
pmid = {40299101},
issn = {1573-4978},
mesh = {Humans ; *Calcitonin Gene-Related Peptide/metabolism/genetics ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Nervous System Diseases/metabolism ; Signal Transduction ; Receptors, Calcitonin Gene-Related Peptide/metabolism ; Oxidative Stress ; },
abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Spinal muscular atrophy (SMA) are neurodegenerative diseases (NDDs) characterized by progressive neuronal degeneration. Recent studies provide compelling information regarding the contribution of Calcitonin Gene-Related Peptide (CGRP), a potent neuropeptide, in regulating neuroinflammation, vasodilation, and neuronal survival in these disorders. This review systematically delves into the multidimensional aspects of CGRP as both a neuroprotective agent and a neurotoxic factor in NDDs. The neuroprotective effects of CGRP include suppression of inflammation, regulation of intracellular signaling pathways, and promotion of neuronal growth and survival. However, under pathological conditions, its overexpression or dysregulation is associated with oxidative stress, excitotoxicity, and neuronal death. The therapeutic use of CGRP and its receptor antagonists in migraine provides substantial evidence for CGRP's therapeutic potential, which can be further explored for the management of NDDs. However, since the bidirectional nature of CGRP effects is evident, it is crucial to gain an accurate insight into its mechanisms to target only the neuropeptide's beneficial effects while completely avoiding the undesired consequences. Further studies should focus on understanding the context-dependent activity of CGRP in the hope of designing targeted therapy for NDDs, which could gradually transform the current pharmacological management of NDDs.},
}

Humans
*Calcitonin Gene-Related Peptide/metabolism/genetics
Animals
Neuroprotective Agents/pharmacology/therapeutic use/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy/pathology
*Nervous System Diseases/metabolism
Signal Transduction
Receptors, Calcitonin Gene-Related Peptide/metabolism
Oxidative Stress

@article {pmid40298821,
year = {2025},
author = {Bortolotti, M and Polito, L and Battelli, MG and Bolognesi, A},
title = {Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/antiox14040483},
pmid = {40298821},
issn = {2076-3921},
abstract = {Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.},
}

@article {pmid40290120,
year = {2025},
author = {Hong, Y and Song, Y and Wang, W and Shi, J and Chen, X},
title = {Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases.},
journal = {Genes & diseases},
volume = {12},
number = {4},
pages = {101437},
pmid = {40290120},
issn = {2352-3042},
abstract = {Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.},
}

@article {pmid40288591,
year = {2025},
author = {Servi, R and Akkoç, RF and Aksu, F and Servi, S},
title = {Therapeutic Potential of Enzymes, Neurosteroids, and Synthetic Steroids in Neurodegenerative Disorders: A Critical Review.},
journal = {The Journal of steroid biochemistry and molecular biology},
volume = {},
number = {},
pages = {106766},
doi = {10.1016/j.jsbmb.2025.106766},
pmid = {40288591},
issn = {1879-1220},
abstract = {Neurodegenerative disorders present a significant challenge to healthcare systems, mainly due to the limited availability of effective treatment options to halt or reverse disease progression. Endogenous steroids synthesized in the central nervous system, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), progesterone (PROG), and allopregnanolone (ALLO), have been identified as potential therapeutic agents for neurodegenerative diseases. Neurosteroids such as ALLO, DHEA, and PROG, as well as their synthetic analogs like Ganaxolene, Fluasterone, and Olexoxime, offer promising effects for conditions such as Alzheimer's disease (AD) and depression. Moreover, Brexanolone and Ganaxolone are synthetic steroids approved for the treatment of postpartum depression and epilepsy, respectively. Neurosteroids such as ALLO are crucial in modulating GABAergic neurotransmission and reducing neuroinflammation. These compounds enhance the activity of GABA-A receptors, leading to increased inhibitory signaling in the brain, which can help regulate mood, cognition, and neuroprotection. Small clinical trials and observational studies indicate that ALLO may have cognitive benefits, but no large-scale, definitive meta-analysis confirms a 20% improvement in AD patients. Mitochondrial dysfunction plays a vital role in the pathogenesis of numerous neurological diseases due to the high-energy demand and sensitivity of neurons to oxidative stress. Reduced mitochondrial function leads to amyloid-beta plaques and tau tangles accumulation in AD. In Parkinson's disease (PD), mitochondrial dysfunction resulting from the PINK1 or Parkin genes leads to energy deficiencies and the accumulation of toxic byproducts. Mutations in genes such as SOD1, C9orf72, and TDP-43 have been associated with mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS). Moreover, studies on these neurodegenerative diseases suggest that inflammation is not merely a consequence of neurodegeneration but is also an essential factor in this process. Many neurological disorders involve multifaceted interactions between genetics, the environment, and immune responses, making it difficult to pinpoint their exact causes. Future research aims to overcome these hurdles through genetic advances, regenerative medicine, and personalized therapies. Cutting-edge technologies such as artificial intelligence and high-throughput screening are expected to accelerate drug discovery and improve diagnostic accuracy. Increasing collaboration between interdisciplinary fields such as bioinformatics, neuroscience, and immunology will lead to innovative treatment strategies. This comprehensive review discusses the therapeutic effects of enzymes, neurosteroids, and synthetic steroids in different neurodegenerative diseases, particularly AD, PD, ALS, and MS. Potential challenges in the therapeutic use of neurosteroids, such as the limited bioavailability and off-target effects of synthetic steroids, are also discussed, and an up-to-date and comprehensive review of the impact of these steroids on neurodegenerative disorders is presented.},
}

@article {pmid40287045,
year = {2025},
author = {Dudzisz, K and Wandzik, I},
title = {Antisense Oligonucleotides: A Promising Advancement in Neurodegenerative Disease Treatment.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {177644},
doi = {10.1016/j.ejphar.2025.177644},
pmid = {40287045},
issn = {1879-0712},
abstract = {Antisense oligonucleotides (ASOs) are a class of therapeutics designed to modulate gene expression and have shown promise in the treatment of various neurodegenerative diseases. As of March 2025, four ASO-based therapies have received approval for the treatment of neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and hereditary transthyretin amyloidosis (ATTR). These approvals underscore the therapeutic potential of ASOs as effective treatments for neurodegenerative diseases by addressing specific genetic abnormalities. This is best demonstrated by clinical studies in more than a dozen ASOs, which could pave the way for the development of new therapeutics soon. Moreover, the ongoing extended clinical studies, which target presymptomatic carriers, have significant potential to cure familial ALS based on the SOD1 gene mutation. This review provides an update on clinical trials, highlighting promising results and the challenges encountered.},
}

@article {pmid40284554,
year = {2025},
author = {Tamai, R and Kiyoura, Y},
title = {Candida Infections: The Role of Saliva in Oral Health-A Narrative Review.},
journal = {Microorganisms},
volume = {13},
number = {4},
pages = {},
pmid = {40284554},
issn = {2076-2607},
support = {21K10233, 23K09511//KAKEN/ ; },
abstract = {Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals.},
}

@article {pmid40283578,
year = {2025},
author = {Mantle, D and Hargreaves, I},
title = {Coenzyme Q10 and the Blood-Brain Barrier: An Overview.},
journal = {Journal of clinical medicine},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/jcm14082748},
pmid = {40283578},
issn = {2077-0383},
abstract = {Mitochondrial dysfunction is a common factor known to be involved in the pathogenesis of a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Given the importance of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, and the deficiency of CoQ10 reported in such neurological disorders, there is a rationale for investigating the potential therapeutic role of supplementary CoQ10. However, while there is evidence for the efficacy of CoQ10 supplementation in animal models of the above disorders, randomised controlled clinical trials supplementing CoQ10 in PD, AD, or ALS have had disappointing outcomes. This in turn may be a reflection of the current uncertainty as to whether CoQ10 can access the blood-brain barrier in human subjects. In an attempt to further elucidate the disparity in outcomes of such preclinical and clinical studies, in this article we have reviewed evidence from the peer-reviewed literature to establish the ability of CoQ10 to access the brain via the BBB.},
}

@article {pmid40283201,
year = {2025},
author = {González-Sánchez, M and Ramírez-Expósito, MJ and Martínez-Martos, JM},
title = {Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
doi = {10.3390/life15040647},
pmid = {40283201},
issn = {2075-1729},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, and respiratory failure. This comprehensive review synthesizes the current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, and evolving therapeutic strategies. Mechanistically, ALS arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), and FUS) and dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, and prion-like propagation of toxic aggregates. Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain. Clinically, ALS intersects with frontotemporal dementia (FTD) in up to 50% of the cases, driven by shared TDP-43 pathology and C9orf72 hexanucleotide expansions. Epidemiological studies have revealed a lifetime risk of 1:350, with male predominance (1.5:1) and peak onset between 50 and 70 years. Disease progression varies widely, with a median survival of 2-4 years post-diagnosis, underscoring the urgency for early intervention. Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. Non-pharmacological treatment advances, such as non-invasive ventilation (NIV), prolong survival by 13 months and improve quality of life, particularly in bulb-involved patients. Multidisciplinary care-integrating physical therapy, respiratory support, nutritional management, and cognitive assessments-is critical to addressing motor and non-motor symptoms (e.g., dysphagia, spasticity, sleep disturbances). Emerging therapies show promise in preclinical models. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies.},
}

@article {pmid40282367,
year = {2025},
author = {Watanabe, Y and Nakagawa, T and Nakagawa, M and Nakayama, K},
title = {The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis.},
journal = {Genes},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/genes16040407},
pmid = {40282367},
issn = {2073-4425},
support = {23K06367//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *NIMA-Related Kinase 1/genetics/metabolism ; *Valosin Containing Protein/genetics/metabolism ; *Cyclins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Animals ; DNA Damage ; Mutation ; DNA Repair ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. Although significant progress has been made in understanding ALS, its molecular mechanisms remain complex and multifactorial. This review explores the potential convergent mechanisms underlying ALS pathogenesis, focusing on the roles of key proteins including NEK1, C21ORF2, cyclin F, VCP, and TDP-43. Recent studies suggest that mutations in C21ORF2 lead to the stabilization of NEK1, while cyclin F mutations activate VCP, resulting in TDP-43 aggregation. TDP-43 aggregation, a hallmark of ALS, impairs RNA processing and protein transport, both of which are essential for neuronal function. Furthermore, TDP-43 has emerged as a key player in DNA damage repair, translocating to DNA damage sites and recruiting repair proteins. Given that NEK1, VCP, and cyclin F are also involved in DNA repair, this review examines how these proteins may intersect to disrupt DNA damage repair mechanisms, contributing to ALS progression. Impaired DNA repair and protein homeostasis are suggested to be central downstream mechanisms in ALS pathogenesis. Ultimately, understanding the interplay between these pathways could offer novel insights into ALS and provide potential therapeutic targets. This review aims to highlight the emerging connections between protein aggregation, DNA damage repair, and cellular dysfunction in ALS, fostering a deeper understanding of its molecular basis and potential avenues for intervention.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*NIMA-Related Kinase 1/genetics/metabolism
*Valosin Containing Protein/genetics/metabolism
*Cyclins/genetics/metabolism
DNA-Binding Proteins/genetics/metabolism
Animals
DNA Damage
Mutation
DNA Repair

@article {pmid40281300,
year = {2025},
author = {Upadhayay, S and Soni, D and Dhureja, M and Temgire, P and Kumar, V and Arthur, R and Kumar, P},
title = {Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40281300},
issn = {1559-1182},
abstract = {In the last few decades, the incidence and progression of neurological disorders have consistently increased, which mainly occur due to environmental pollution, genetic abnormalities, and modern lifestyles. Several case reports suggested that these factors enhanced oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, leading to neurological disease. The pathophysiology of neurological disorders is still not understood, mainly due to the diversity within affected populations. Existing treatment options primarily provide symptomatic relief but frequently come with considerable side effects, including depression, anxiety, and restlessness. Fibroblast growth factors (FGFs) are key signalling molecules regulating various cellular functions, including cell proliferation, differentiation, electrical excitability, and injury responses. Hence, several investigations claimed a relationship between FGFs and neurological disorders, and their findings indicated that they could be used as therapeutic targets for neurological disorders. The FGFs are reported to activate various signalling pathways, including Ras/MAPK/PI3k/Akt, and downregulate the GSK-3β/NF-κB pathways responsible for anti-oxidant, anti-inflammatory, and anti-apoptotic effects. Therefore, researchers are interested in developing novel treatment options for neurological disorders. The emergence of unreported FGFs contributes to our understanding of their involvement in these conditions and encourages further exploration of innovative therapeutic approaches. All the data were obtained from published articles using PubMed, Web of Science, and Scopus databases using the search terms Fibroblast Growth Factor, PD, HD, AD, ALS, signalling pathways, and neurological disorders.},
}

@article {pmid40280271,
year = {2025},
author = {Kopalli, SR and Behl, T and Baldaniya, L and Ballal, S and Joshi, KK and Arya, R and Chaturvedi, B and Chauhan, AS and Verma, R and Patel, M and Jain, SK and Wal, A and Gulati, M and Koppula, S},
title = {Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111375},
doi = {10.1016/j.pnpbp.2025.111375},
pmid = {40280271},
issn = {1878-4216},
abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target.},
}

@article {pmid40279084,
year = {2025},
author = {Singh, P and Borkar, M and Doshi, G},
title = {Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {40279084},
issn = {1573-501X},
abstract = {Aging is a slow and irreversible biological process leading to decreased cell and tissue functions with higher risks of multiple age-related diseases, including neurodegenerative diseases. It is widely accepted that aging represents the leading risk factor for neurodegeneration. The pathogenesis of these diseases involves complex interactions of genetic mutations, environmental factors, oxidative stress, neuroinflammation, and mitochondrial dysfunction, which complicate treatment with traditional mono-targeted therapies. Network pharmacology can help identify potential gene or protein targets related to neurodegenerative diseases. Integrating advanced molecular profiling technologies and computer-aided drug design further enhances the potential of network pharmacology, enabling the identification of biomarkers and therapeutic targets, thus paving the way for precision medicine in neurodegenerative diseases. This review article delves into the application of network pharmacology in understanding and treating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and spinal muscular atrophy. Overall, this article emphasizes the importance of addressing aging as a central factor in developing effective disease-modifying therapies, highlighting how network pharmacology can unravel the complex biological networks associated with aging and pave the way for personalized medical strategies.},
}

@article {pmid40278411,
year = {2025},
author = {Di Sarno, A and Romano, F and Arianna, R and Serpico, D and Lavorgna, M and Savastano, S and Colao, A and Di Somma, C},
title = {Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.},
journal = {Metabolites},
volume = {15},
number = {4},
pages = {},
pmid = {40278411},
issn = {2218-1989},
abstract = {Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer's disease (AD), Parkisons's disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue.},
}

@article {pmid40273110,
year = {2025},
author = {Souza, AA and Silva, STD and Régis, AMP and Aires, DN and Pondofe, KM and Melo, LP and Valentim, RAM and Lindquist, ARR and Macedo, LRD and Ribeiro, TS},
title = {Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0320788},
pmid = {40273110},
issn = {1932-6203},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; *Muscle Strength/physiology ; *Resistance Training/methods ; *Exercise Therapy/methods ; },
abstract = {Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy
*Muscle Strength/physiology
*Resistance Training/methods
*Exercise Therapy/methods

@article {pmid40272376,
year = {2025},
author = {Nguyen, THV and Ferron, F and Murakami, K},
title = {Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.5c00153},
pmid = {40272376},
issn = {1554-8937},
abstract = {Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.},
}

@article {pmid39778593,
year = {2025},
author = {Chen, Q and Chen, G and Wang, Q},
title = {Application of Network Pharmacology in the Treatment of Neurodegenerative Diseases with Traditional Chinese Medicine.},
journal = {Planta medica},
volume = {91},
number = {5},
pages = {226-237},
pmid = {39778593},
issn = {1439-0221},
support = {2023AFB677//the Natural Science Foundation of Hubei Province/ ; 2024AFB578//the Natural Science Foundation of Hubei Province/ ; 2023LYYYGZRP0003//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; 2023LYYYSZRP0001//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; },
mesh = {Humans ; *Medicine, Chinese Traditional/methods ; *Neurodegenerative Diseases/drug therapy ; *Network Pharmacology/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; },
abstract = {In recent years, the incidence of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has exhibited a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese medicine, with its multicomponent and multitarget characteristics, offers a promising approach to treating neurodegenerative diseases. However, comprehensively elucidating the complex mechanisms underlying traditional Chinese medicine formulations remains challenging. As an emerging systems biology method, network pharmacology has provided a vital tool for revealing the multitarget mechanisms of traditional Chinese medicine through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases using traditional Chinese medicine, analyzes the current status of relevant databases and technological methods, discusses the limitations, and proposes future directions to promote the modernization of traditional Chinese medicine and the development of precision medicine.},
}

Humans
*Medicine, Chinese Traditional/methods
*Neurodegenerative Diseases/drug therapy
*Network Pharmacology/methods
*Drugs, Chinese Herbal/pharmacology/therapeutic use

@article {pmid40271431,
year = {2025},
author = {Rana, A and Katiyar, A and Arun, A and Berrios, JN and Kumar, G},
title = {Natural sulfur compounds in mental health and neurological disorders: insights from observational and intervention studies.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1534000},
doi = {10.3389/fnut.2025.1534000},
pmid = {40271431},
issn = {2296-861X},
abstract = {Over the years, the global disease burden of neurological disorders (NDs) and mental disorders (MDs) has significantly increased, making them one of the most critical concerns and challenges to human health. In pursuit of novel therapies against MD and ND, there has been a growing focus on nutrition and health. Dietary sulfur, primarily derived from various natural sources, plays a crucial role in numerous physiological processes, including brain function. This review offers an overview of the chemical composition of several natural sources of the sulfur-rich substances such as isothiocyanates, sulforaphane, glutathione, taurine, sulfated polysaccharides, allyl sulfides, and sulfur-containing amino acids, all of which have neuroprotective properties. A multitude of studies have documented that consuming foods that are high in sulfur enhances brain function by improving cognitive parameters and reduces the severity of neuropathology by exhibiting antioxidant and anti-inflammatory properties at the molecular level. In addition, the growing role of natural sulfur compounds in repairing endothelial dysfunction, compromising blood-brain barrier and improving cerebral blood flow, are documented here. Furthermore, this review covers the encouraging results of supplementing sulfur-rich diets in many animal models and clinical investigations, along with their molecular targets in MD, such as schizophrenia, depression, anxiety, bipolar disorder, and autism spectrum disorder, and ND, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). The prospects of natural sulfur compounds show great promise as they have potential applications in nutraceuticals, medicines, and functional foods to enhance brain function and prevent diseases. However, additional research is required to clarify the mechanisms by which it works, enhance its bioavailability, and evaluate its long-term safety for broad use.},
}

@article {pmid40271071,
year = {2025},
author = {Luo, H and Wei, S and Fu, S and Han, L},
title = {Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1511011},
doi = {10.3389/fphar.2025.1511011},
pmid = {40271071},
issn = {1663-9812},
abstract = {Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.},
}

@article {pmid39254482,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {1-2},
pages = {48-57},
doi = {10.1080/21678421.2024.2400522},
pmid = {39254482},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/economics ; Humans ; *Muscular Atrophy, Spinal/drug therapy/economics ; },
abstract = {INTRODUCTION: The therapeutic options for spinal muscular atrophy (SMA) are encouraging. However, there is currently no cure for amyotrophic lateral sclerosis (ALS). The clinical and economic uncertainty surrounding innovative treatments for rare neurodegenerative diseases makes it necessary to understand managed entry agreements (MEAs). The aim of this study was to review whether models of MEAs in SMA could be extrapolated to ALS.

METHODS: We performed a scoping review with information on MEAs on SMA in Web of Science (WOS), PubMed, Lyfegen Library, the National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH).

RESULTS: We found 45 results in WOS and PubMed. After an initial survey, 10 were reviewed to assess eligibility, and three were selected. We obtained 44 results from Lyfegen Library, and three results each from NICE and CADTH.

CONCLUSION: The main objective of MEAs is to reduce uncertainty in the financing of drugs with a high budgetary impact and clinical concerns, as is the case with drugs for SMA and ALS. While the information available on MEAs in SMA is scarce, some conceptual models are publicly available. MEAs for long-term treatments for SMA could be used for the design of MEAs in ALS because of their similarities in economic and clinical uncertainty.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/economics
Humans
*Muscular Atrophy, Spinal/drug therapy/economics

@article {pmid40268233,
year = {2025},
author = {Basak, B and Holzbaur, ELF},
title = {Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169161},
doi = {10.1016/j.jmb.2025.169161},
pmid = {40268233},
issn = {1089-8638},
abstract = {Mitochondrial quality control is instrumental in regulating neuronal health and survival. The receptor-mediated clearance of damaged mitochondria by autophagy, known as mitophagy, plays a key role in controlling mitochondrial homeostasis. Mutations in genes that regulate mitophagy are causative for familial forms of neurological disorders including Parkinson's disease (PD) and Amyotrophic lateral sclerosis(ALS). PINK1/Parkin-dependent mitophagy is the best studied mitophagy pathway, while more recent work has brought to light additional mitochondrial quality control mechanisms that operate either in parallel to or independent of PINK1/Parkin mitophagy. Here, we discuss our current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis. We also summarize progress in our understanding of the links between mitophagic dysfunction and neurodegeneration and highlight the potential for therapeutic interventions to maintain mitochondrial health and neuronal function.},
}

@article {pmid40265276,
year = {2025},
author = {Mendonça, IP and Peixoto, CA},
title = {The Double-Edged Sword: The Complex Function of Enteric Glial Cells in Neurodegenerative Diseases.},
journal = {Journal of neurochemistry},
volume = {169},
number = {4},
pages = {e70069},
doi = {10.1111/jnc.70069},
pmid = {40265276},
issn = {1471-4159},
support = {CNPq;#301891/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; IAM-PROEP# 005-FIO-22//Instituto Aggeu Magalhães/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism ; *Neuroglia/metabolism/pathology/physiology ; Animals ; *Enteric Nervous System/pathology/metabolism ; },
abstract = {Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut-brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/pathology/metabolism
*Neuroglia/metabolism/pathology/physiology
Animals
*Enteric Nervous System/pathology/metabolism

@article {pmid40256588,
year = {2024},
author = {Ahmady, H and Afrand, M and Motaqi, M and Meftahi, GH},
title = {Utilizing Sertoli Cell Transplantation as a Therapeutic Technique for the Management of Neurodegenerative Diseases.},
journal = {Archives of Razi Institute},
volume = {79},
number = {4},
pages = {701-710},
pmid = {40256588},
issn = {2008-9872},
mesh = {*Neurodegenerative Diseases/therapy ; Humans ; Male ; Animals ; *Sertoli Cells/transplantation ; },
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are defined by aberrant protein accumulation, brain atrophy, and gradual decline of neuronal function. Despite the considerable endeavors devoted to discovering treatments for NDs in recent decades, the demand for efficient therapeutic agents persists. Sertoli cells (SCs) play a crucial role in providing a supportive structure and environment for the development of germ cells. SCs, whether transplanted as xenogeneic or allogeneic cells, present a viable choice for enhancing graft persistence via the release of immunomodulatory and trophic factors, including neurturin (NTN), platelet-derived growth factor, Fas (CD95) ligand (FasL), glial-derived neurotrophic factor, interleukin 1 (IL1), brain-derived neurotrophic factor, interleukin 6 (IL6), transforming growth factors, and vascular growth factor, that protect replaced cells and tissues from the immune system. However, there is currently no cohesive evidence regarding the neuroprotective influence of the transplantation of SCs on NDs. Therefore, this review focuses on assessing stem cells' neuroprotective impact on neurodegenerative diseases in pre-clinical settings and presenting cohesive information. A comprehensive search was conducted between 2000 and 2022. In the identification stage, after a comprehensive search across databases, including Web of Science, Scopus, and PubMed/Medline, 103 papers were obtained. The search conducted in the present study yielded a total of nine relevant papers on the therapeutic effect of the transplantation of SCs on NDs. It was found that the transplantation of SCs exhibits a promising impact on enhancing the symptoms of neurological diseases in rats. The findings highlight the need for multiple standardized pre-clinical trials to find reliable information to confirm the utilization of the transplantation of SCs and the reduction of the symptoms of neurodegenerative diseases.},
}

*Neurodegenerative Diseases/therapy
Humans
Male
Animals
*Sertoli Cells/transplantation