@article {pmid38745425,
year = {2024},
author = {Nona, RJ and Henderson, RD and McCombe, PA},
title = {Neutrophil-to-lymphocyte ratio at diagnosis as a biomarker for survival of amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {25},
number = {5-6},
pages = {452-464},
doi = {10.1080/21678421.2024.2351187},
pmid = {38745425},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; Humans ; *Neutrophils ; *Lymphocytes ; Female ; Male ; Biomarkers/blood ; Middle Aged ; Aged ; },
abstract = {INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has previously been reported to be associated with survival in ALS. To provide further information about the role of NLR as a biomarker in ALS, we performed a systematic review, analyzed data from our local cohort of ALS subjects and performed a meta-analysis.

METHODS: (1) The systematic review used established methods. (2) Using data from our cohort of subjects, we analyzed the association of NLR with survival. (3) Meta-analysis was performed using previous studies and our local data.

RESULTS: (1) In the systematic review, higher NLR was associated with shorter survival in all studies. (2) In our subjects, survival was significantly shorter in patients in the highest NLR groups. (3) Meta-analysis showed subjects with highest NLR tertile or with NLR >3 had significantly shorter survival than other subjects.

DISCUSSION: This study supports NLR as a biomarker in ALS; high NLR is associated with poor survival.},
}

*Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality
Humans
*Neutrophils
*Lymphocytes
Female
Male
Biomarkers/blood
Middle Aged
Aged

@article {pmid38666601,
year = {2024},
author = {Officer, L and Armon, C and Barkhaus, P and Beauchamp, M and Benatar, M and Bertorini, T and Bowser, R and Bromberg, M and Brown, A and Carbunar, OM and Carter, GT and Crayle, J and Denson, K and Feldman, E and Fullam, T and Heiman-Patterson, T and Jackson, C and Jhooty, S and Levinson, D and Li, X and Linares, A and Mallon, E and Mascias Cadavid, J and Mcdermott, C and Mushannen, T and Ostrow, L and Patel, R and Pattee, G and Ratner, D and Sun, Y and Sladky, J and Wicks, P and Bedlack, R},
title = {ALSUntangled #75: Portable neuromodulation stimulator therapy.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {25},
number = {5-6},
pages = {648-652},
doi = {10.1080/21678421.2024.2346825},
pmid = {38666601},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Electric Stimulation Therapy/methods/instrumentation ; },
abstract = {Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy
*Electric Stimulation Therapy/methods/instrumentation

@article {pmid38561605,
year = {2024},
author = {Singh, K and Gupta, JK and Kumar, S and Soni, U},
title = {A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.},
journal = {Current protein & peptide science},
volume = {25},
number = {7},
pages = {507-526},
pmid = {38561605},
issn = {1875-5550},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Peptides/therapeutic use/chemistry/pharmacology ; Animals ; Alzheimer Disease/drug therapy/metabolism/pathology ; Parkinson Disease/drug therapy/metabolism/pathology ; Neuroprotective Agents/therapeutic use/pharmacology/chemistry ; Oxidative Stress/drug effects ; Huntington Disease/drug therapy/metabolism/pathology ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Cholinesterase Inhibitors/therapeutic use/pharmacology/chemistry ; },
abstract = {Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Peptides/therapeutic use/chemistry/pharmacology
Animals
Alzheimer Disease/drug therapy/metabolism/pathology
Parkinson Disease/drug therapy/metabolism/pathology
Neuroprotective Agents/therapeutic use/pharmacology/chemistry
Oxidative Stress/drug effects
Huntington Disease/drug therapy/metabolism/pathology
Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology
Cholinesterase Inhibitors/therapeutic use/pharmacology/chemistry

@article {pmid37691199,
year = {2024},
author = {Bhat, MA and Dhaneshwar, S},
title = {Neurodegenerative Diseases: New Hopes and Perspectives.},
journal = {Current molecular medicine},
volume = {24},
number = {8},
pages = {1004-1032},
pmid = {37691199},
issn = {1875-5666},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; Animals ; },
abstract = {Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Friedrich ataxia are all incurable neurodegenerative diseases defined by the continuous progressive loss of distinct neuronal subtypes. Despite their rising prevalence among the world's ageing population, fewer advances have been made in the concurrent massive efforts to develop newer drugs. Recently, there has been a shift in research focus towards the discovery of new therapeutic agents for neurodegenerative diseases. In this review, we have summarized the recently developed therapies and their status in the management of neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/therapy/pathology
Animals

@article {pmid38318827,
year = {2024},
author = {Motamedy, S and Soltani, B and Kameshki, H and Alipour Kermani, A and Saboori Amleshi, R and Nazeri, M and Shabani, M},
title = {The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex[®] - A Cannabis-derived Spray.},
journal = {Mini reviews in medicinal chemistry},
volume = {24},
number = {15},
pages = {1427-1448},
pmid = {38318827},
issn = {1875-5607},
mesh = {Humans ; *Neuroprotective Agents/pharmacology/chemistry ; *Cannabidiol/pharmacology/therapeutic use/chemistry ; *Plant Extracts/chemistry/pharmacology ; *Dronabinol/pharmacology/chemistry/therapeutic use ; Animals ; Multiple Sclerosis/drug therapy ; Cannabis/chemistry ; Drug Combinations ; },
abstract = {Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.},
}

Humans
*Neuroprotective Agents/pharmacology/chemistry
*Cannabidiol/pharmacology/therapeutic use/chemistry
*Plant Extracts/chemistry/pharmacology
*Dronabinol/pharmacology/chemistry/therapeutic use
Animals
Multiple Sclerosis/drug therapy
Cannabis/chemistry
Drug Combinations

@article {pmid37622689,
year = {2024},
author = {Dey, B and Kumar, A and Patel, AB},
title = {Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.},
journal = {Current neuropharmacology},
volume = {22},
number = {11},
pages = {1778-1806},
pmid = {37622689},
issn = {1875-6190},
support = {DST/CSRI/2017/258//Department of Science and Technology (DST), Govt. of India/ ; DBT/JRF/BET-17/1/2017/AL/400//Department of Biotechnology (DBT), Govt. of India/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Animals ; Gene-Environment Interaction ; Motor Neurons/metabolism/pathology ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common, adult-onset, progressive motor neurodegenerative disorder that results in death within 3 years of the clinical diagnosis. Due to the clinicopathological heterogeneity, any reliable biomarkers for diagnosis or prognosis of ALS have not been identified till date. Moreover, the only three clinically approved treatments are not uniformly effective in slowing the disease progression. Over the last 15 years, there has been a rapid advancement in research on the complex pathomechanistic landscape of ALS that has opened up new avenues for successful clinical translation of targeted therapeutics. Multiple studies suggest that the age-dependent interaction of risk-associated genes with environmental factors and endogenous modifiers is critical to the multi-step process of ALS pathogenesis. In this review, we provide an updated discussion on the dysregulated cross-talk between intracellular homeostasis processes, the unique molecular networks across selectively vulnerable cell types, and the multisystemic nature of ALS pathomechanisms. Importantly, this work highlights the alteration in epigenetic and epitranscriptomic landscape due to gene-environment interactions, which have been largely overlooked in the context of ALS pathology. Finally, we suggest that precision medicine research in ALS will be largely benefitted from the stratification of patient groups based on the clinical phenotype, onset and progression, genome, exposome, and metabolic identities.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
Animals
Gene-Environment Interaction
Motor Neurons/metabolism/pathology

@article {pmid39006715,
year = {2024},
author = {Suleiman Khoury, Z and Sohail, F and Wang, J and Mendoza, M and Raake, M and Tahoor Silat, M and Reddy Bathinapatta, M and Sadeghzadegan, A and Meghana, P and Paul, J},
title = {Neuroinflammation: A Critical Factor in Neurodegenerative Disorders.},
journal = {Cureus},
volume = {16},
number = {6},
pages = {e62310},
pmid = {39006715},
issn = {2168-8184},
abstract = {This review offers a comprehensive review of the signals and the paramount role neuroinflammation plays in neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The study explores the sophisticated interactions between microglial, astrocytic, and dendritic cells and how neuroinflammation affects long-term neuronal damage and dysfunction. There are specific pathways related to the mentioned inflammatory processes, including Janus kinases/signal transducer and activator of transcriptions, nuclear factor-κB, and mitogen-activated protein kinases pathways. Neuroinflammation is argued to be a double-edged sword, being not only a protective agent that prevents further neuron damage but also the causative factor in more cell injury development. This concept of contrasting inflammation with neuroprotection advocates for the use of therapeutic techniques that seek to modulate neuroinflammatory responses as part of the neurodegeneration treatment. The recent research findings are integrated with the established knowledge to help present a comprehensive image of neuroinflammation's impact on neurodegenerative diseases and its implications for future therapy.},
}

@article {pmid39000336,
year = {2024},
author = {Bodai, L and Borosta, R and Ferencz, Á and Kovács, M and Zsindely, N},
title = {The Role of miR-137 in Neurodegenerative Disorders.},
journal = {International journal of molecular sciences},
volume = {25},
number = {13},
pages = {},
pmid = {39000336},
issn = {1422-0067},
support = {OTKA 145898//National Research, Development and Innovation Office [Hungary]/ ; },
mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; Gene Expression Regulation ; },
abstract = {Neurodegenerative diseases affect an increasing part of the population of modern societies, burdening healthcare systems and causing immense suffering at the personal level. The pathogenesis of several of these disorders involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. microRNAs (miRNAs) are short non-coding RNA molecules that modulate gene expression by suppressing the translation of partially complementary mRNAs. miR-137 is a conserved, neuronally enriched miRNA that is implicated in neurodegeneration. Here, we review the current body of knowledge about the role that miR-137 plays in five prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The presented data indicate that, rather than having a general neuroprotective role, miR-137 modulates the pathology of distinct disorders differently.},
}

*MicroRNAs/genetics/metabolism
Humans
*Neurodegenerative Diseases/genetics/metabolism
Animals
Gene Expression Regulation

@article {pmid38999371,
year = {2024},
author = {Dell'Anna, G and Fanti, L and Fanizza, J and Barà, R and Barchi, A and Fasulo, E and Elmore, U and Rosati, R and Annese, V and Laterza, L and Fuccio, L and Azzolini, F and Danese, S and Mandarino, FV},
title = {VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review.},
journal = {Journal of clinical medicine},
volume = {13},
number = {13},
pages = {},
pmid = {38999371},
issn = {2077-0383},
abstract = {Esophagectomy, while a pivotal treatment for esophageal cancer, is not without adverse events. Among these, anastomotic leak (AL) is the most feared complication, threatening patient lives and incurring significant healthcare costs. The management of AL is complex and lacks standardization. Given the high morbidity and mortality rates associated with redo-surgery, which poses risks for already fragile patients, various endoscopic treatments have been developed over time. Self-expandable metallic stents (SEMSs) were the most widely used treatment until the early 2000s. The mechanism of action of SEMSs includes covering the wall defect, protecting it from secretions, and promoting healing. In 2010, endoscopic vacuum therapy (EVT) emerged as a viable alternative for treating ALs, quickly gaining acceptance in clinical practice. EVT involves placing a dedicated sponge under negative pressure inside or adjacent to the wall defect, aiming to clear the leak and promote granulation tissue formation. More recently, the VAC-Stent entered the scenario of endoscopic treatment of post-esophagectomy ALs. This device combines a fully covered SEMS with an integrated EVT sponge, blending the ability of SEMSs to exclude defects and maintain the patency of the esophageal lumen with the capacity of EVT to aspirate secretions and promote the formation of granulation tissue. Although the literature on this new device is not extensive, early results from the application of VAC-Stent have shown promising outcomes. This review aims to synthesize the preliminary efficacy and safety data on the device, thoroughly analyze its advantages over traditional techniques and disadvantages, explore areas for improvement, and propose future directions.},
}

@article {pmid38988889,
year = {2024},
author = {Ansari, U and Alam, M and Nadora, D and Muttalib, Z and Chen, V and Taguinod, I and FitzPatrick, M and Wen, J and Ansari, Z and Lui, F},
title = {Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.},
journal = {AIMS neuroscience},
volume = {11},
number = {2},
pages = {166-177},
pmid = {38988889},
issn = {2373-7972},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition.},
}

@article {pmid38976599,
year = {2024},
author = {Xu, Z and Xu, R},
title = {Current potential diagnostic biomarkers of amyotrophic lateral sclerosis.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {38976599},
issn = {2191-0200},
abstract = {Amyotrophic lateral sclerosis (ALS) currently lacks the useful diagnostic biomarkers. The current diagnosis of ALS is mainly depended on the clinical manifestations, which contributes to the diagnostic delay and be difficult to make the accurate diagnosis at the early stage of ALS, and hinders the clinical early therapeutics. The more and more pathogenesis of ALS are found at the last 30 years, including excitotoxicity, the oxidative stress, the mitochondrial dysfunction, neuroinflammation, the altered energy metabolism, the RNA misprocessing and the most recent neuroimaging findings. The findings of these pathogenesis bring the new clues for searching the diagnostic biomarkers of ALS. At present, a large number of relevant studies about the diagnostic biomarkers are underway. The ALS pathogenesis related to the diagnostic biomarkers might lessen the diagnostic reliance on the clinical manifestations. Among them, the cortical altered signatures of ALS patients derived from both structural and functional magnetic resonance imaging and the emerging proteomic biomarkers of neuronal loss and glial activation in the cerebrospinal fluid as well as the potential biomarkers in blood, serum, urine, and saliva are leading a new phase of biomarkers. Here, we reviewed these current potential diagnostic biomarkers of ALS.},
}

@article {pmid38837229,
year = {2024},
author = {Ó Murchú, SC and O'Halloran, KD},
title = {BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy.},
journal = {The Journal of physiology},
volume = {602},
number = {14},
pages = {3255-3272},
doi = {10.1113/JP280280},
pmid = {38837229},
issn = {1469-7793},
support = {SFI FFP/19/6628 INSPIRE DMD/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {*Muscular Dystrophy, Duchenne/physiopathology/therapy ; Humans ; *Hypoxia/physiopathology ; Animals ; Respiration ; },
abstract = {Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disorder, characterised by progressive decline in skeletal muscle function due to the secondary consequences of dystrophin deficiency. Weakness extends to the respiratory musculature, and cardiorespiratory failure is the leading cause of death in men with DMD. Intermittent hypoxia has emerged as a potential therapy to counteract ventilatory insufficiency by eliciting long-term facilitation of breathing. Mechanisms of sensory and motor facilitation of breathing have been well delineated in animal models. Various paradigms of intermittent hypoxia have been designed and implemented in human trials culminating in clinical trials in people with spinal cord injury and amyotrophic lateral sclerosis. Application of therapeutic intermittent hypoxia to DMD is considered together with discussion of the potential barriers to progression owing to the complexity of this devastating disease. Notwithstanding the considerable challenges and potential pitfalls of intermittent hypoxia-based therapies for DMD, we suggest it is incumbent on the research community to explore the potential benefits in pre-clinical models. Intermittent hypoxia paradigms should be implemented to explore the proclivity to express respiratory plasticity with the longer-term aim of preserving and potentiating ventilation in pre-clinical models and people with DMD.},
}

*Muscular Dystrophy, Duchenne/physiopathology/therapy
Humans
*Hypoxia/physiopathology
Animals
Respiration

@article {pmid38975145,
year = {2024},
author = {Zhang, J and Xie, D and Jiao, D and Zhou, S and Liu, S and Ju, Z and Hu, L and Qi, L and Yao, C and Zhao, C},
title = {From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.},
journal = {Heliyon},
volume = {10},
number = {12},
pages = {e32688},
pmid = {38975145},
issn = {2405-8440},
abstract = {The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.},
}

@article {pmid38973130,
year = {2024},
author = {Corcia, P and Guy, N and Pradat, PF and Soriani, MH and Verschueren, A and Couratier, P},
title = {Treatment continuity of amyotrophic lateral sclerosis with available riluzole formulations: state of the art and current challenges in a 'real-world' setting.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2024.2375330},
pmid = {38973130},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare multisystem neurodegenerative disease leading to death due to respiratory failure. Riluzole was the first disease modifying treatment approved in ALS. Randomized clinical trials showed a significant benefit of riluzole on survival in the months following randomization, with a good safety profile. 'Real-world' studies suggested that the survival benefit of riluzole is substantially greater, with an extended survival ranging between 6 and 19 months. The main limiting associated adverse effects of riluzole are non-severe gastrointestinal complications and an elevation of liver enzymes, observed in 10% of patients. While different classes of drugs have been approved in some countries, riluzole remains the gold standard of therapy. Dysphagia induced by ALS is a major challenge for food intake and riluzole administration. Tablet crushing is associated with a loss of drug intake and a risk of powder aspiration, which jeopardizes the benefits of riluzole. Riluzole oral suspension (ROS) and oral film (ROF) allow riluzole intake in patients with dysphagia. Both formulations are bioequivalent to riluzole tablets with a good safety profile albeit transient oral hypoaesthesia. In case of severe dysphagia, ROS can be used with percutaneous endoscopic gastrostomy. ROF, the last approved formulation, requires low swallowing capacities and may contribute to maintain the efficacy of riluzole when tablets are inadequate according to patient's status and/or preferences. To optimize treatment continuity in newly diagnosed patients, the expected psychological impact of formulation switching that may be perceived as the sign of disease progression should be anticipated.},
}

@article {pmid38969143,
year = {2024},
author = {Jha, SK and Nelson, VK and Suryadevara, PR and Panda, SP and Pullaiah, CP and Nuli, MV and Kamal, M and Imran, M and Ausali, S and Abomughaid, MM and Srivastava, R and Deka, R and Pritam, P and Gupta, N and Shyam, H and Singh, IK and Pandey, BW and Dewanjee, S and Jha, NK and Jafari, SM},
title = {Cannabidiol and Neurodegeneration: From Molecular Mechanisms to Clinical Benefits.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102386},
doi = {10.1016/j.arr.2024.102386},
pmid = {38969143},
issn = {1872-9649},
abstract = {Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce malfunction of psycho-motor functions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of its associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. Cannabidiol has gained attention as a promising therapeutic drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as its clinical applications in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.},
}

@article {pmid38760935,
year = {2024},
author = {Fiadeiro, MB and Diogo, JC and Silva, AA and Kim, YS and Cristóvão, AC},
title = {NADPH Oxidases in Neurodegenerative Disorders: Mechanisms and Therapeutic Opportunities.},
journal = {Antioxidants & redox signaling},
volume = {},
number = {},
pages = {},
doi = {10.1089/ars.2023.0002},
pmid = {38760935},
issn = {1557-7716},
abstract = {Significance: The nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme family, located in the central nervous system, is recognized as a source of reactive oxygen species (ROS) in the brain. Despite its importance in cellular processes, excessive ROS generation leads to cell death and is involved in the pathogenesis of neurodegenerative disorders. Recent advances: NOX enzymes contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke, highlighting their potential as targets for future therapeutic development. This review will discuss NOX's contribution and therapeutic targeting potential in neurodegenerative diseases, focusing on PD, AD, ALS, and stroke. Critical issues: Homeostatic and physiological levels of ROS are crucial for regulating several processes, such as development, memory, neuronal signaling, and vascular homeostasis. However, NOX-mediated excessive ROS generation is deeply involved in the damage of DNA, proteins, and lipids, leading to cell death in the pathogenesis of a wide range of diseases, namely neurodegenerative diseases. Future directions: It is essential to understand the role of NOX homologs in neurodegenerative disorders and the pathological mechanisms undergoing neurodegeneration mediated by increased levels of ROS. This further knowledge will allow the development of new specific NOX inhibitors and their application for neurodegenerative disease therapeutics.},
}

@article {pmid38802624,
year = {2024},
author = {Riva, N and Domi, T and Pozzi, L and Lunetta, C and Schito, P and Spinelli, EG and Cabras, S and Matteoni, E and Consonni, M and Bella, ED and Agosta, F and Filippi, M and Calvo, A and Quattrini, A},
title = {Update on recent advances in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {271},
number = {7},
pages = {4693-4723},
pmid = {38802624},
issn = {1432-1459},
support = {IDEALS//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; Marazzina Project//Marazzina Foundation/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; },
abstract = {In the last few years, our understanding of disease molecular mechanisms underpinning ALS has advanced greatly, allowing the first steps in translating into clinical practice novel research findings, including gene therapy approaches. Similarly, the recent advent of assistive technologies has greatly improved the possibility of a more personalized approach to supportive and symptomatic care, in the context of an increasingly complex multidisciplinary line of actions, which remains the cornerstone of ALS management. Against this rapidly growing background, here we provide an comprehensive update on the most recent studies that have contributed towards our understanding of ALS pathogenesis, the latest results from clinical trials as well as the future directions for improving the clinical management of ALS patients.},
}

*Amyotrophic Lateral Sclerosis/therapy/genetics
Humans
Animals

@article {pmid38967881,
year = {2024},
author = {Rojas-López, JC and Estrada-Gualdron, PI and Ramírez-Guerrero, S and Velásquez-Cárdenas, MJ and Redondo-Escobar, J and Vargas-Arenas, S and Palacios-Sánchez, L and Palacios-Espinosa, X},
title = {Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {38967881},
issn = {1590-3478},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.},
}

@article {pmid38967655,
year = {2024},
author = {Müller, P and Draguhn, A and Egorov, AV},
title = {Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.},
journal = {Pflugers Archiv : European journal of physiology},
volume = {},
number = {},
pages = {},
pmid = {38967655},
issn = {1432-2013},
support = {HE8155/1-2//Deutsche Forschungsgemeinschaft/ ; EG134/2-1//Deutsche Forschungsgemeinschaft/ ; Treat-ION01GM1907A//Bundesministerium für Bildung und Forschung/ ; College for Clinician Scientists//Else Kröner-Fresenius-Stiftung/ ; },
abstract = {Persistent sodium current (INaP) is an important activity-dependent regulator of neuronal excitability. It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of INaP are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of INaP and for developing new therapeutic strategies. However, the literature on INaP is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on INaP, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used INaP blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded bona fide INaP blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.},
}

@article {pmid38966756,
year = {2024},
author = {Garg, V and Geurten, BRH},
title = {Diving deep: zebrafish models in motor neuron degeneration research.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1424025},
pmid = {38966756},
issn = {1662-4548},
abstract = {In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion-zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.},
}

@article {pmid38504592,
year = {2024},
author = {Hamilton, HL and Akther, M and Anis, S and Colwell, CB and Vargas, MR and Pehar, M},
title = {Nicotinamide Adenine Dinucleotide Precursor Supplementation Modulates Neurite Complexity and Survival in Motor Neurons from Amyotrophic Lateral Sclerosis Models.},
journal = {Antioxidants & redox signaling},
volume = {},
number = {},
pages = {},
doi = {10.1089/ars.2023.0360},
pmid = {38504592},
issn = {1557-7716},
support = {R01 NS089640/NS/NINDS NIH HHS/United States ; R01 NS100835/NS/NINDS NIH HHS/United States ; },
abstract = {Aims: Increasing nicotinamide adenine dinucleotide (NAD[+]) availability has been proposed as a therapeutic approach to prevent neurodegeneration in amyotrophic lateral sclerosis (ALS). Accordingly, NAD[+] precursor supplementation appears to exert neuroprotective effects in ALS patients and mouse models. The mechanisms mediating neuroprotection remain uncertain but could involve changes in multiple cell types. We investigated a potential direct effect of the NAD[+] precursor nicotinamide mononucleotide (NMN) on the health of cultured induced pluripotent stem cell (iPSC)-derived human motor neurons and in motor neurons isolated from two ALS mouse models, that is, mice overexpressing wild-type transactive response DNA binding protein-43 (TDP-43) or the ALS-linked human superoxide dismutase 1 with the G93A mutation (hSOD1[G93A]). Results: NMN treatment increased the complexity of neuronal processes in motor neurons isolated from both mouse models and in iPSC-derived human motor neurons. In addition, NMN prevented neuronal death induced by trophic factor deprivation. In mouse and human motor neurons expressing ALS-linked mutant superoxide dismutase 1, NMN induced an increase in glutathione levels, but this effect was not observed in nontransgenic or TDP-43 overexpressing motor neurons. In contrast, NMN treatment normalized the TDP-43 cytoplasmic mislocalization induced by its overexpression. Innovation: NMN can directly act on motor neurons to increase the growth and complexity of neuronal processes and prevent the death induced by trophic factor deprivation. Conclusion: Our results support a direct beneficial effect of NAD[+] precursor supplementation on the maintenance of the neuritic arbor in motor neurons. Importantly, this was observed in motor neurons isolated from two different ALS models, with and without involvement of TDP-43 pathology, supporting its therapeutic potential in sporadic and familial ALS.},
}

@article {pmid38965379,
year = {2024},
author = {Jacob, SM and Lee, S and Kim, SH and Sharkey, KA and Pfeffer, G and Nguyen, MD},
title = {Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {38965379},
issn = {1759-4766},
abstract = {Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.},
}

@article {pmid38963497,
year = {2024},
author = {Yu, G and Bai, Y and Zhang, ZY},
title = {Valosin-Containing Protein (VCP)/p97 Oligomerization.},
journal = {Sub-cellular biochemistry},
volume = {104},
number = {},
pages = {485-501},
pmid = {38963497},
issn = {0306-0225},
mesh = {*Valosin Containing Protein/metabolism/genetics/chemistry ; Humans ; Protein Multimerization ; Animals ; Mutation ; Frontotemporal Dementia/genetics/metabolism ; Adenosine Triphosphatases/metabolism/genetics/chemistry ; Osteitis Deformans/genetics/metabolism ; Cell Cycle Proteins/metabolism/genetics/chemistry ; Myositis, Inclusion Body/genetics/metabolism ; Muscular Dystrophies, Limb-Girdle ; },
abstract = {Valosin-containing protein (VCP), also known as p97, is an evolutionarily conserved AAA+ ATPase essential for cellular homeostasis. Cooperating with different sets of cofactors, VCP is involved in multiple cellular processes through either the ubiquitin-proteasome system (UPS) or the autophagy/lysosomal route. Pathogenic mutations frequently found at the interface between the NTD domain and D1 ATPase domain have been shown to cause malfunction of VCP, leading to degenerative disorders including the inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS), and cancers. Therefore, VCP has been considered as a potential therapeutic target for neurodegeneration and cancer. Most of previous studies found VCP predominantly exists and functions as a hexamer, which unfolds and extracts ubiquitinated substrates from protein complexes for degradation. However, recent studies have characterized a new VCP dodecameric state and revealed a controlling mechanism of VCP oligomeric states mediated by the D2 domain nucleotide occupancy. Here, we summarize our recent knowledge on VCP oligomerization, regulation, and potential implications of VCP in cellular function and pathogenic progression.},
}

*Valosin Containing Protein/metabolism/genetics/chemistry
Humans
Protein Multimerization
Animals
Mutation
Frontotemporal Dementia/genetics/metabolism
Adenosine Triphosphatases/metabolism/genetics/chemistry
Osteitis Deformans/genetics/metabolism
Cell Cycle Proteins/metabolism/genetics/chemistry
Myositis, Inclusion Body/genetics/metabolism
Muscular Dystrophies, Limb-Girdle

@article {pmid38788085,
year = {2024},
author = {Mohassel, P and Abdullah, M and Eichler, FS and Dunn, TM},
title = {Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.},
journal = {Journal of neuromuscular diseases},
volume = {11},
number = {4},
pages = {735-747},
doi = {10.3233/JND-240014},
pmid = {38788085},
issn = {2214-3602},
mesh = {Humans ; *Serine C-Palmitoyltransferase/metabolism/genetics ; *Neurodevelopmental Disorders ; *Neurodegenerative Diseases/metabolism ; *Hereditary Sensory and Autonomic Neuropathies/genetics/metabolism/physiopathology ; Spastic Paraplegia, Hereditary/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Sphingolipids/metabolism ; },
abstract = {Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.},
}

Humans
*Serine C-Palmitoyltransferase/metabolism/genetics
*Neurodevelopmental Disorders
*Neurodegenerative Diseases/metabolism
*Hereditary Sensory and Autonomic Neuropathies/genetics/metabolism/physiopathology
Spastic Paraplegia, Hereditary/genetics/metabolism
Amyotrophic Lateral Sclerosis/genetics/metabolism
Sphingolipids/metabolism

@article {pmid38747014,
year = {2024},
author = {Gale, J and Aizenman, E},
title = {The physiological and pathophysiological roles of copper in the nervous system.},
journal = {The European journal of neuroscience},
volume = {60},
number = {1},
pages = {3505-3543},
doi = {10.1111/ejn.16370},
pmid = {38747014},
issn = {1460-9568},
support = {5T32AG021885/NH/NIH HHS/United States ; NS043277/NH/NIH HHS/United States ; 5T32AG021885/NH/NIH HHS/United States ; NS043277/NH/NIH HHS/United States ; },
mesh = {Humans ; *Copper/metabolism ; Animals ; Homeostasis/physiology ; Nervous System/metabolism ; },
abstract = {Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-β-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.},
}

Humans
*Copper/metabolism
Animals
Homeostasis/physiology
Nervous System/metabolism

@article {pmid38451707,
year = {2024},
author = {Clayton, EL and Huggon, L and Cousin, MA and Mizielinska, S},
title = {Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {147},
number = {7},
pages = {2289-2307},
doi = {10.1093/brain/awae074},
pmid = {38451707},
issn = {1460-2156},
support = {//UK Dementia Research Institute/ ; //UK Medical Research Council/ ; /ALZS_/Alzheimer's Society/United Kingdom ; //Alzheimer's Research UK/ ; 204954/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; P2003//Epilepsy Research UK/ ; 529508//Simons Foundation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology ; *Frontotemporal Dementia/genetics/pathology/physiopathology ; *Synapses/pathology ; *Presynaptic Terminals/pathology/metabolism ; Animals ; Mutation ; },
abstract = {Frontotemporal dementia and amyotrophic lateral sclerosis are common forms of neurodegenerative disease that share overlapping genetics and pathologies. Crucially, no significantly disease-modifying treatments are available for either disease. Identifying the earliest changes that initiate neuronal dysfunction is important for designing effective intervention therapeutics. The genes mutated in genetic forms of frontotemporal dementia and amyotrophic lateral sclerosis have diverse cellular functions, and multiple disease mechanisms have been proposed for both. Identification of a convergent disease mechanism in frontotemporal dementia and amyotrophic lateral sclerosis would focus research for a targetable pathway, which could potentially effectively treat all forms of frontotemporal dementia and amyotrophic lateral sclerosis (both familial and sporadic). Synaptopathies are diseases resulting from physiological dysfunction of synapses, and define the earliest stages in multiple neuronal diseases, with synapse loss a key feature in dementia. At the presynapse, the process of synaptic vesicle recruitment, fusion and recycling is necessary for activity-dependent neurotransmitter release. The unique distal location of the presynaptic terminal means the tight spatio-temporal control of presynaptic homeostasis is dependent on efficient local protein translation and degradation. Recently, numerous publications have shown that mutations associated with frontotemporal dementia and amyotrophic lateral sclerosis present with synaptopathy characterized by presynaptic dysfunction. This review will describe the complex local signalling and membrane trafficking events that occur at the presynapse to facilitate neurotransmission and will summarize recent publications linking frontotemporal dementia/amyotrophic lateral sclerosis genetic mutations to presynaptic function. This evidence indicates that presynaptic synaptopathy is an early and convergent event in frontotemporal dementia and amyotrophic lateral sclerosis and illustrates the need for further research in this area, to identify potential therapeutic targets with the ability to impact this convergent pathomechanism.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology
*Frontotemporal Dementia/genetics/pathology/physiopathology
*Synapses/pathology
*Presynaptic Terminals/pathology/metabolism
Animals
Mutation

@article {pmid38960473,
year = {2024},
author = {R, HC and Datta, A and S, UK and Zayed, H and D, TK and C, GPD},
title = {Decoding genetic and pathophysiological mechanisms in amyotrophic lateral sclerosis and primary lateral sclerosis: A comparative study of differentially expressed genes and implicated pathways in motor neuron disorders.},
journal = {Advances in protein chemistry and structural biology},
volume = {141},
number = {},
pages = {177-201},
doi = {10.1016/bs.apcsb.2023.12.008},
pmid = {38960473},
issn = {1876-1631},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Motor Neuron Disease/genetics/metabolism ; Gene Expression Profiling ; },
abstract = {Motor Neuron Disorders (MNDs), characterized by the degradation and loss of function of motor neurons, are recognized as fatal conditions with limited treatment options and no known cure. The present study aimed to identify the pathophysiological functions and affected genes in patients with MNDs, specifically Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). The GSE56808 dataset comprised three sample groups: six patients diagnosed with ALS (GSM1369650, GSM1369652, GSM1369654, GSM1369656, GSM1369657, GSM1369658), five patients diagnosed with PLS (GSM1369648, GSM1369649, GSM1369653, GSM1369655, GSM1369659), and six normal controls (GSM1369642, GSM1369643, GSM1369644, GSM1369645, GSM1369646, and GSM1369647). The application of computational analysis of microarray gene expression profiles enabled us to identify 346 significantly differentially expressed genes (DEGs), 169 genes for the ALS sample study, and 177 genes for the PLS sample study. Enrichment was carried out using MCODE, a Cytoscape plugin. Functional annotation of DEGs was carried out via ClueGO/CluePedia (v2.5.9) and further validated via the DAVID database. NRP2, SEMA3D, ROBO3 and, CACNB1, CACNG2 genes were identified as the gene of interest for ALS and PLS sample groups, respectively. Axonal guidance (GO:0007411) and calcium ion transmembrane transport (GO:0070588) were identified to be some of the significantly dysregulated gene ontology (GO) terms, with arrhythmogenic right ventricular cardiomyopathy (KEGG:05412) to be the top relevant KEGG pathway which is affected in MND patients. ROBO3 gene was observed to have distinctive roles in ALS and PLS-affected patients, hinting towards the differential progression of ALS from PLS. The insights derived from our comprehensive analysis accentuate the distinct variances in the underlying molecular pathogenesis of ALS and PLS. Further research should investigate the mechanistic roles of the identified DEGs and molecular pathways, leading to potential targeted therapies for ALS and PLS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Motor Neuron Disease/genetics/metabolism
Gene Expression Profiling

@article {pmid38944367,
year = {2024},
author = {Wankhede, NL and Rajendra Kopalli, S and Dhokne, MD and Badnag, DJ and Chandurkar, PA and Mangrulkar, SV and Shende, PV and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Koppula, S and Kale, MB},
title = {Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health.},
journal = {Mitochondrion},
volume = {78},
number = {},
pages = {101926},
doi = {10.1016/j.mito.2024.101926},
pmid = {38944367},
issn = {1872-8278},
abstract = {Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.},
}

@article {pmid38942541,
year = {2024},
author = {Shukla, H and John, D and Banerjee, S and Tiwari, AK},
title = {Drug repurposing for neurodegenerative diseases.},
journal = {Progress in molecular biology and translational science},
volume = {207},
number = {},
pages = {249-319},
doi = {10.1016/bs.pmbts.2024.03.035},
pmid = {38942541},
issn = {1878-0814},
mesh = {Humans ; *Drug Repositioning ; *Neurodegenerative Diseases/drug therapy ; Animals ; },
abstract = {Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.},
}

Humans
*Drug Repositioning
*Neurodegenerative Diseases/drug therapy
Animals

@article {pmid38933502,
year = {2024},
author = {Chen, BR and Wu, T and Chen, TH and Wang, Y},
title = {Neuroimmune interactions and their roles in neurodegenerative diseases.},
journal = {Fundamental research},
volume = {4},
number = {2},
pages = {251-261},
pmid = {38933502},
issn = {2667-3258},
abstract = {The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.},
}

@article {pmid38928874,
year = {2024},
author = {Szulc, A and Wiśniewska, K and Żabińska, M and Gaffke, L and Szota, M and Olendzka, Z and Węgrzyn, G and Pierzynowska, K},
title = {Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases.},
journal = {Foods (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/foods13121931},
pmid = {38928874},
issn = {2304-8158},
support = {533-0C20-GS0D-24//University of Gdansk/ ; },
abstract = {Over the past decades, there has been a significant increase in the burden of neurological diseases, including neurodegenerative disorders, on a global scale. This is linked to a widespread demographic trend in which developed societies are aging, leading to an increased proportion of elderly individuals and, concurrently, an increase in the number of those afflicted, posing one of the main public health challenges for the coming decades. The complex pathomechanisms of neurodegenerative diseases and resulting varied symptoms, which differ depending on the disease, environment, and lifestyle of the patients, make searching for therapies for this group of disorders a formidable challenge. Currently, most neurodegenerative diseases are considered incurable. An important aspect in the fight against and prevention of neurodegenerative diseases may be broadly understood lifestyle choices, and more specifically, what we will focus on in this review, a diet. One proposal that may help in the fight against the spread of neurodegenerative diseases is a diet rich in flavonoids. Flavonoids are compounds widely found in products considered healthy, such as fruits, vegetables, and herbs. Many studies indicated not only the neuroprotective effects of these compounds but also their ability to reverse changes occurring during the progression of diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. Here, we present the main groups of flavonoids, discussing their characteristics and mechanisms of action. The most widely described mechanisms point to neuroprotective functions due to strong antioxidant and anti-inflammatory effects, accompanied with their ability to penetrate the blood-brain barrier, as well as the ability to inhibit the formation of protein aggregates. The latter feature, together with promoting removal of the aggregates is especially important in neurodegenerative diseases. We discuss a therapeutic potential of selected flavonoids in the fight against neurodegenerative diseases, based on in vitro studies, and their impact when included in the diet of animals (laboratory research) and humans (population studies). Thus, this review summarizes flavonoids' actions and impacts on neurodegenerative diseases. Therapeutic use of these compounds in the future is potentially possible but depends on overcoming key challenges such as low bioavailability, determining the therapeutic dose, and defining what a flavonoid-rich diet is and determining its potential negative effects. This review also suggests further research directions to address these challenges.},
}

@article {pmid38928553,
year = {2024},
author = {Di Martino, P and Marcozzi, V and Bibbò, S and Ghinassi, B and Di Baldassarre, A and Gaggi, G and Di Credico, A},
title = {Unraveling the Epigenetic Landscape: Insights into Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.},
journal = {Brain sciences},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/brainsci14060553},
pmid = {38928553},
issn = {2076-3425},
support = {MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, Developmental Neurotoxi-city of Endocrine Disruptors from Plastic Pollutants.//NextGenerationEU "MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, De-velopmental Neurotoxicity of Endocrine Disruptors from Plastic Pollutants./ ; },
abstract = {Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.},
}

@article {pmid38927681,
year = {2024},
author = {Adler, GL and Le, K and Fu, Y and Kim, WS},
title = {Human Endogenous Retroviruses in Neurodegenerative Diseases.},
journal = {Genes},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/genes15060745},
pmid = {38927681},
issn = {2073-4425},
mesh = {Humans ; *Endogenous Retroviruses/genetics/pathogenicity ; *Neurodegenerative Diseases/virology/genetics ; Amyotrophic Lateral Sclerosis/virology/genetics ; Animals ; },
abstract = {Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated in the pathogenesis of neurodegenerative diseases, a group of CNS diseases characterized by a progressive loss of structure and function of neurons, resulting in cell death and multiple physiological dysfunctions. Much evidence indicates that HERVs are initiators or drivers of neurodegenerative processes in multiple sclerosis and amyotrophic lateral sclerosis, and clinical trials have been designed to target HERVs. In recent years, the role of HERVs has been explored in other major neurodegenerative diseases, including frontotemporal dementia, Alzheimer's disease and Parkinson's disease, with some interesting discoveries. This review summarizes and evaluates the past and current research on HERVs in neurodegenerative diseases. It discusses the potential role of HERVs in disease manifestation and neurodegeneration. It critically reviews antiretroviral strategies used in the therapeutic intervention of neurodegenerative diseases.},
}

Humans
*Endogenous Retroviruses/genetics/pathogenicity
*Neurodegenerative Diseases/virology/genetics
Amyotrophic Lateral Sclerosis/virology/genetics
Animals

@article {pmid38927674,
year = {2024},
author = {Gotte, G},
title = {Effects of Pathogenic Mutants of the Neuroprotective RNase 5-Angiogenin in Amyotrophic Lateral Sclerosis (ALS).},
journal = {Genes},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/genes15060738},
pmid = {38927674},
issn = {2073-4425},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; *Ribonuclease, Pancreatic/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; Animals ; Mutation ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic aggregates. However, efficacious therapeutic approaches are still lacking. Notably, heterozygous missense mutations affecting the gene coding for RNase 5, an enzyme also called angiogenin (ANG), were found to favor ALS onset. This is also true for the less-studied but angiogenic RNase 4. This review reports the substrate targets and illustrates the neuroprotective role of native ANG in the neo-vascularization of motoneurons. Then, it discusses the molecular determinants of many pathogenic ANG mutants, which almost always cause loss of function related to ALS, resulting in failures in angiogenesis and motoneuron protection. In addition, ANG mutations are sometimes combined with variants of other factors, thereby potentiating ALS effects. However, the activity of the native ANG enzyme should be finely balanced, and not excessive, to avoid possible harmful effects. Considering the interplay of these angiogenic RNases in many cellular processes, this review aims to stimulate further investigations to better elucidate the consequences of mutations in ANG and/or RNase 4 genes, in order to achieve early diagnosis and, possibly, successful therapies against ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology
Humans
*Ribonuclease, Pancreatic/genetics/metabolism
*Motor Neurons/metabolism/pathology
Animals
Mutation

@article {pmid38921286,
year = {2024},
author = {Katz, L and Gur, A},
title = {Psychosocial Intervention for Family Caregivers of ALS Patients: A Systematic Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {38921286},
issn = {2227-9032},
abstract = {PROPOSAL: This systematic review aims to comprehensively examine all existing knowledge on psychosocial interventions for family caregivers for ALS patients. Also, the study will present the gaps in knowledge, recommendations for future research, and guidelines for psychosocial interventions that are focused and adapted to the needs of family caregivers of ALS patients.

MATERIALS AND METHODS: The systematic review was conducted according to the PRISMA guidelines and identified studies on psychosocial intervention for family caregivers of ALS patients, using five electronic databases: PsychNET, PubMed, EBSCO, PRIMO, and PROQUEST. Seven articles met the criteria and were included in the review. A thematic analysis was conducted to extract major themes.

RESULTS: Three major themes emerged from the data: (1) Personal benefits; (2) Interpersonal benefits; and (3) Charting challenges and pathways to improve psychosocial interventions.

CONCLUSIONS: Based on the findings, practical guidelines were formulated that focus on the group's composition, the facilitator's role, the contents, the relationships within the group, and the opportunities and limitations of online interventions.},
}

@article {pmid38921029,
year = {2024},
author = {Carata, E and Muci, M and Di Giulio, S and Di Giulio, T and Mariano, S and Panzarini, E},
title = {The Neuromuscular Disorder Mediated by Extracellular Vesicles in Amyotrophic Lateral Sclerosis.},
journal = {Current issues in molecular biology},
volume = {46},
number = {6},
pages = {5999-6017},
doi = {10.3390/cimb46060358},
pmid = {38921029},
issn = {1467-3045},
abstract = {Amyotrophic lateral sclerosis (ALS) represents a neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons, resulting in muscular atrophy and eventual paralysis. While much research has concentrated on investigating the impact of major mutations associated with ALS on motor neurons and central nervous system (CNS) cells, recent studies have unveiled that ALS pathogenesis extends beyond CNS imbalances, encompassing dysregulation in other tissues such as skeletal muscle. Evidence from animal models and patients supports this broader perspective. Skeletal muscle, once considered solely as an effector organ, is now recognized as possessing significant secretory activity capable of influencing motor neuron survival. However, the precise cellular and molecular mechanisms underlying the detrimental effects observed in muscle and its associated structures in ALS remain poorly understood. Additionally, emerging data suggest that extracellular vesicles (EVs) may play a role in the establishment and function of the neuromuscular junction (NMJ) under both physiological and pathological conditions and in wasting and regeneration of skeletal muscles, particularly in neurodegenerative diseases like ALS. This review aims to explore the key findings about skeletal muscle involvement in ALS, shedding light on the potential underlying mechanisms and contributions of EVs and their possible application for the design of biosensors.},
}

@article {pmid38726604,
year = {2024},
author = {López Gómez, JJ and Díaz Marín, C and Castillo-García, T and Larrad-Sainz, A and Gastaldo-Simeón, R and Juarros-Martínez, S and Leunda-Eizmendi, L and Civera Andrés, M and Matía Martín, P},
title = {[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review].},
journal = {Nutricion hospitalaria},
volume = {41},
number = {3},
pages = {712-723},
doi = {10.20960/nh.05189},
pmid = {38726604},
issn = {1699-5198},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; Female ; *Nutrition Therapy/methods ; *Malnutrition/etiology/therapy ; Middle Aged ; Nutritional Status ; },
abstract = {Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications
Female
*Nutrition Therapy/methods
*Malnutrition/etiology/therapy
Middle Aged
Nutritional Status

@article {pmid38920997,
year = {2024},
author = {Nowak, I and Paździor, M and Sarna, R and Madej, M},
title = {Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.},
journal = {Current issues in molecular biology},
volume = {46},
number = {6},
pages = {5436-5453},
doi = {10.3390/cimb46060325},
pmid = {38920997},
issn = {1467-3045},
abstract = {Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.},
}

@article {pmid38920691,
year = {2024},
author = {Ilieva, MS},
title = {Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis.},
journal = {Cells},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/cells13121063},
pmid = {38920691},
issn = {2073-4409},
mesh = {Humans ; *RNA, Untranslated/genetics/metabolism ; *Nervous System Diseases/genetics/metabolism ; *Mental Disorders/genetics/metabolism ; RNA, Circular/genetics/metabolism ; Animals ; RNA, Long Noncoding/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/genetics/metabolism ; },
abstract = {Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape.},
}

Humans
*RNA, Untranslated/genetics/metabolism
*Nervous System Diseases/genetics/metabolism
*Mental Disorders/genetics/metabolism
RNA, Circular/genetics/metabolism
Animals
RNA, Long Noncoding/genetics/metabolism
Gene Expression Regulation
MicroRNAs/genetics/metabolism

@article {pmid38918327,
year = {2024},
author = {Sharma, V and Sharma, P and Singh, TG},
title = {Mechanistic insights on TLR-4 mediated inflammatory pathway in neurodegenerative diseases.},
journal = {Pharmacological reports : PR},
volume = {},
number = {},
pages = {},
pmid = {38918327},
issn = {2299-5684},
abstract = {Neurodegenerative diseases (NDDs) pose a significant issue in healthcare, needing a thorough knowledge of their complex molecular mechanisms. A diverse set of cell signaling mediators and their interactions play critical roles in neuroinflammation. The release of pro-inflammatory mediators in response to neural dysfunction is detrimental to normal cell survival. Moreover, the important role of nuclear factor-κB (NF-κB) in the central nervous system through Toll-like receptor (TLR) activation has been well established. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the interactions between novel pharmacological agents (TLR-4/NF-κB inhibitors) and neurodegeneration encompassing Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis and stroke. Insights garnered from this exploration underscore the potential of TLR-4 as a therapeutic target. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. This review thus serves as a roadmap, guiding future research endeavors toward innovative strategies for combatting the complex interplay between TLR-4 signaling and NDDs.},
}

@article {pmid38915767,
year = {2024},
author = {Ambrosini, A and Dalla Bella, E and Ravasi, M and Melazzini, M and Lauria, G},
title = {New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1407912},
pmid = {38915767},
issn = {2296-858X},
abstract = {Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis. The difficulties encountered are discussed as an example of the barriers that academics involved in this type of study may face. Although further development of the drug for this target population was hampered for several reasons, the study was successful in many ways. Firstly, because the hypothesis tested was confirmed in a sub-population, leading to alternative innovative solutions that are now under clinical investigation. In addition, the study was informative and provided new insights into the disease, which are now giving new impetus to laboratory research. The message from this example is that even a repurposing study with an old product has the potential to generate innovation and interest from industry partners, provided it is based on a sound rationale, the study design is adequate to ensure meaningful results, and the investigators keep the full clinical development picture in mind.},
}

@article {pmid38813817,
year = {2024},
author = {Sprunger, ML and Jackrel, ME},
title = {The role of Matrin-3 in physiology and its dysregulation in disease.},
journal = {Biochemical Society transactions},
volume = {52},
number = {3},
pages = {961-972},
doi = {10.1042/BST20220585},
pmid = {38813817},
issn = {1470-8752},
mesh = {Humans ; *RNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Nuclear Matrix-Associated Proteins/metabolism ; *Frontotemporal Dementia/metabolism/genetics ; DNA-Binding Proteins/metabolism ; Animals ; DNA Damage ; RNA-Binding Protein FUS/metabolism/chemistry ; },
abstract = {The dysfunction of many RNA-binding proteins (RBPs) that are heavily disordered, including TDP-43 and FUS, are implicated in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These proteins serve many important roles in the cell, and their capacity to form biomolecular condensates (BMCs) is key to their function, but also a vulnerability that can lead to misregulation and disease. Matrin-3 (MATR3) is an intrinsically disordered RBP implicated both genetically and pathologically in ALS/FTD, though it is relatively understudied as compared with TDP-43 and FUS. In addition to binding RNA, MATR3 also binds DNA and is implicated in many cellular processes including the DNA damage response, transcription, splicing, and cell differentiation. It is unclear if MATR3 localizes to BMCs under physiological conditions, which is brought further into question due to its lack of a prion-like domain. Here, we review recent studies regarding MATR3 and its roles in numerous physiological processes, as well as its implication in a range of diseases.},
}

Humans
*RNA-Binding Proteins/metabolism
*Amyotrophic Lateral Sclerosis/metabolism/genetics
*Nuclear Matrix-Associated Proteins/metabolism
*Frontotemporal Dementia/metabolism/genetics
DNA-Binding Proteins/metabolism
Animals
DNA Damage
RNA-Binding Protein FUS/metabolism/chemistry

@article {pmid38713169,
year = {2024},
author = {Nikel, LM and Talbot, K and Vahsen, BF},
title = {Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {46},
number = {7},
pages = {e2400054},
doi = {10.1002/bies.202400054},
pmid = {38713169},
issn = {1521-1878},
support = {2023/MNDS/6400/753TALB//MND Scotland/ ; Talbot/Apr22/889-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Humans ; *Microglia/metabolism/pathology ; *Motor Neurons/pathology/metabolism ; Coculture Techniques ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
*Induced Pluripotent Stem Cells/metabolism
Humans
*Microglia/metabolism/pathology
*Motor Neurons/pathology/metabolism
Coculture Techniques
Animals

@article {pmid38914810,
year = {2024},
author = {Manchia, M and Paribello, P and Pinna, M and Steardo, L and Carpiniello, B and Pinna, F and Pisanu, C and Squassina, A and Hajek, T},
title = {Lithium and its effects: does dose matter?.},
journal = {International journal of bipolar disorders},
volume = {12},
number = {1},
pages = {23},
pmid = {38914810},
issn = {2194-7511},
abstract = {BACKGROUND: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.

CONTENT: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.

CONCLUSIONS: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.},
}

@article {pmid38914784,
year = {2024},
author = {Sang, A and Zhuo, S and Bochanis, A and Manautou, JE and Bahal, R and Zhong, XB and Rasmussen, TP},
title = {Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.},
journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy},
volume = {},
number = {},
pages = {},
pmid = {38914784},
issn = {1179-190X},
support = {R35GM140862/GM/NIGMS NIH HHS/United States ; R01HL147028/HL/NHLBI NIH HHS/United States ; },
abstract = {Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].},
}

@article {pmid38898687,
year = {2024},
author = {Lee, B and Lee, SM and Song, JW and Choi, JW},
title = {Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.},
journal = {Biomolecules & therapeutics},
volume = {32},
number = {4},
pages = {403-423},
doi = {10.4062/biomolther.2024.009},
pmid = {38898687},
issn = {1976-9148},
abstract = {The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.},
}

@article {pmid38909349,
year = {2024},
author = {Ketabforoush, A and Faghihi, F and Azedi, F and Ariaei, A and Habibi, MA and Khalili, M and Ashtiani, BH and Joghataei, MT and Arnold, WD},
title = {Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.},
journal = {Clinical drug investigation},
volume = {},
number = {},
pages = {},
pmid = {38909349},
issn = {1179-1918},
abstract = {The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.},
}

@article {pmid38908196,
year = {2024},
author = {Donders, Z and Skorupska, IJ and Willems, E and Mussen, F and Broeckhoven, JV and Carlier, A and Schepers, M and Vanmierlo, T},
title = {Beyond PDE4 inhibition: A comprehensive review on downstream cAMP signaling in the central nervous system.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {177},
number = {},
pages = {117009},
doi = {10.1016/j.biopha.2024.117009},
pmid = {38908196},
issn = {1950-6007},
abstract = {Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown that increased cAMP levels in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating cAMP levels through PDE inhibition provides a therapeutic approach for multiple CNS disorders, including multiple sclerosis, stroke, spinal cord injury, amyotrophic lateral sclerosis, traumatic brain injury, and Alzheimer's disease. In particular, inhibition of the cAMP-specific PDE4 subfamily is widely studied because of its high expression in the CNS. So far, the clinical translation of full PDE4 inhibitors has been hampered because of dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon PDE4 inhibition presents a promising strategy, offering novel and pharmacologically safe targets for treating CNS disorders. Yet, the underlying downstream signaling pathways activated upon PDE(4) inhibition remain partially elusive. This review provides a comprehensive overview of the existing knowledge regarding downstream mediators of cAMP signaling induced by PDE4 inhibition or cAMP stimulators. Furthermore, we highlight existing gaps and future perspectives that may incentivize additional downstream research concerning PDE(4) inhibition, thereby providing novel therapeutic approaches for CNS disorders.},
}

@article {pmid38904729,
year = {2024},
author = {Portes E Silva, KR and Nogueira, EM and Jesus Mendes, AL and Pena, ALB and Simões E Silva, AC},
title = {The potential role of renin angiotensin system in acute leukemia: a narrative review.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {775},
pmid = {38904729},
issn = {1573-4978},
support = {304496/2023-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
mesh = {Humans ; *Renin-Angiotensin System/physiology ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology ; *Angiotensin II/metabolism ; Leukemia, Myeloid, Acute/metabolism/pathology ; Signal Transduction ; Angiotensin I/metabolism ; Neovascularization, Pathologic/metabolism ; Animals ; Peptide Fragments/metabolism ; },
abstract = {Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.},
}

Humans
*Renin-Angiotensin System/physiology
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology
*Angiotensin II/metabolism
Leukemia, Myeloid, Acute/metabolism/pathology
Signal Transduction
Angiotensin I/metabolism
Neovascularization, Pathologic/metabolism
Animals
Peptide Fragments/metabolism

@article {pmid38903602,
year = {2024},
author = {Al-Kuraishy, HM and Jabir, MS and Sulaiman, GM and Mohammed, HA and Al-Gareeb, AI and Albuhadily, AK and Jawad, SF and Swelum, AA and Abomughaid, MM},
title = {The role of statins in amyotrophic lateral sclerosis: protective or not?.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1422912},
pmid = {38903602},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.},
}

@article {pmid38834164,
year = {2024},
author = {Griñán-Ferré, C and Bellver-Sanchis, A and Guerrero, A and Pallàs, M},
title = {Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy.},
journal = {Pharmacological research},
volume = {205},
number = {},
pages = {107247},
doi = {10.1016/j.phrs.2024.107247},
pmid = {38834164},
issn = {1096-1186},
mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/drug therapy/genetics ; *Pharmacogenetics/methods ; *Epigenesis, Genetic/drug effects ; Animals ; Epigenomics/methods ; },
abstract = {About 80 % of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.},
}

Humans
*Precision Medicine/methods
*Neurodegenerative Diseases/drug therapy/genetics
*Pharmacogenetics/methods
*Epigenesis, Genetic/drug effects
Animals
Epigenomics/methods

@article {pmid38898538,
year = {2024},
author = {Bravo-Miana, RDC and Arizaga-Echebarria, JK and Otaegui, D},
title = {Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?.},
journal = {Translational neurodegeneration},
volume = {13},
number = {1},
pages = {32},
pmid = {38898538},
issn = {2047-9158},
support = {PI20/1253//Instituto de Salud Carlos III/ ; KK-2021/00009//Departamento de Desarrollo Económico, Sostenibilidad y Medio Ambiente/ ; ECTRIMS Postdoctoral Research Fellowship 2023//European Committee for Treatment and Research in Multiple Sclerosis/ ; Predoctoral fellowship//Basque Government/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/blood ; *Central Nervous System/metabolism ; *Neurodegenerative Diseases/blood/diagnosis/metabolism ; Animals ; },
abstract = {The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.},
}

Humans
*Extracellular Vesicles/metabolism
*Biomarkers/blood
*Central Nervous System/metabolism
*Neurodegenerative Diseases/blood/diagnosis/metabolism
Animals

@article {pmid38898231,
year = {2024},
author = {Gao, J and Gunasekar, S and Xia, ZJ and Shalin, K and Jiang, C and Chen, H and Lee, D and Lee, S and Pisal, ND and Luo, JN and Griciuc, A and Karp, JM and Tanzi, R and Joshi, N},
title = {Gene therapy for CNS disorders: modalities, delivery and translational challenges.},
journal = {Nature reviews. Neuroscience},
volume = {},
number = {},
pages = {},
pmid = {38898231},
issn = {1471-0048},
abstract = {Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only to tailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders.},
}

@article {pmid38898006,
year = {2024},
author = {Nógrádi, B and Nógrádi-Halmi, D and Erdélyi-Furka, B and Kádár, Z and Csont, T and Gáspár, R},
title = {Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation.},
journal = {Cell death discovery},
volume = {10},
number = {1},
pages = {291},
pmid = {38898006},
issn = {2058-7716},
support = {BO/00574/22//Magyar Tudományos Akadémia (Hungarian Academy of Sciences)/ ; ÚNKP-23-5 -SZTE-711//Emberi Eroforrások Minisztériuma (Ministry of Human Capacities)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. Loss of motoneurons and pyramidal cells is thought to be the center piece of the complex and multifaceted ALS pathology, however, the exact mechanisms laying behind motoneuronal cell death in the spinal cord and motor cortex are still unknown. It was originally proposed that apoptosis plays a fundamental role in motoneuronal demise, nonetheless, later it became clear that other forms of regulated cell death, including necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, may also contribute to motoneuron loss. Over the past years, multiple studies aimed to improve our understanding of the contributory role of these mechanisms as well as to offer novel targets for potential therapeutic interventions. The pharmacological inhibition of the ferroptotic pathway and the modulation of the autophagic machinery seem to have particularly promising effects, reducing motoneuron loss and slowing disease progression in transgenic models of ALS. Nevertheless, the potential beneficial effects of necroptosis-targeting interventions were mostly disproven in the latest studies. In this review we aim to summarize the current view on regulated cell death mechanisms that lead to motoneuronal and pyramidal cell degeneration in ALS and showcase their applicability as future drug targets.},
}

@article {pmid38892250,
year = {2024},
author = {Cerantonio, A and Citrigno, L and Greco, BM and De Benedittis, S and Passarino, G and Maletta, R and Qualtieri, A and Montesanto, A and Spadafora, P and Cavalcanti, F},
title = {The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38892250},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *DNA, Mitochondrial/genetics ; *DNA Copy Number Variations ; *Mitochondria/genetics/metabolism ; Huntington Disease/genetics/pathology ; Animals ; },
abstract = {Neurodegenerative diseases are progressive disorders that affect the central nervous system (CNS) and represent the major cause of premature death in the elderly. One of the possible determinants of neurodegeneration is the change in mitochondrial function and content. Altered levels of mitochondrial DNA copy number (mtDNA-CN) in biological fluids have been reported during both the early stages and progression of the diseases. In patients affected by neurodegenerative diseases, changes in mtDNA-CN levels appear to correlate with mitochondrial dysfunction, cognitive decline, disease progression, and ultimately therapeutic interventions. In this review, we report the main results published up to April 2024, regarding the evaluation of mtDNA-CN levels in blood samples from patients affected by Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The aim is to show a probable link between mtDNA-CN changes and neurodegenerative disorders. Understanding the causes underlying this association could provide useful information on the molecular mechanisms involved in neurodegeneration and offer the development of new diagnostic approaches and therapeutic interventions.},
}

Humans
*Neurodegenerative Diseases/genetics
*DNA, Mitochondrial/genetics
*DNA Copy Number Variations
*Mitochondria/genetics/metabolism
Huntington Disease/genetics/pathology
Animals

@article {pmid38891774,
year = {2024},
author = {Arnold, FJ and Putka, AF and Raychaudhuri, U and Hsu, S and Bedlack, RS and Bennett, CL and La Spada, AR},
title = {Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38891774},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Glutamic Acid/metabolism ; Animals ; Motor Neurons/metabolism/pathology ; Aging/metabolism ; Receptors, AMPA/metabolism ; Endoplasmic Reticulum Stress ; Mitochondria/metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Astrocytes/metabolism ; Reactive Oxygen Species/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies for ALS, particularly for sporadic ALS of unknown and diverse etiologies, we must identify key, convergent mechanisms of disease pathogenesis. This review focuses on the origin and effects of glutamate-mediated excitotoxicity in ALS (the cortical hyperexcitability hypothesis), in which increased glutamatergic signaling causes motor neurons to become hyperexcitable and eventually die. We characterize both primary and secondary contributions to excitotoxicity, referring to processes taking place at the synapse and within the cell, respectively. 'Primary pathways' include upregulation of calcium-permeable AMPA receptors, dysfunction of the EAAT2 astrocytic glutamate transporter, increased release of glutamate from the presynaptic terminal, and reduced inhibition by cortical interneurons-all of which have been observed in ALS patients and model systems. 'Secondary pathways' include changes to mitochondrial morphology and function, increased production of reactive oxygen species, and endoplasmic reticulum (ER) stress. By identifying key targets in the excitotoxicity cascade, we emphasize the importance of this pathway in the pathogenesis of ALS and suggest that intervening in this pathway could be effective for developing therapies for this disease.},
}

*Amyotrophic Lateral Sclerosis/metabolism/pathology
Humans
*Glutamic Acid/metabolism
Animals
Motor Neurons/metabolism/pathology
Aging/metabolism
Receptors, AMPA/metabolism
Endoplasmic Reticulum Stress
Mitochondria/metabolism
Excitatory Amino Acid Transporter 2/metabolism
Astrocytes/metabolism
Reactive Oxygen Species/metabolism

@article {pmid38891112,
year = {2024},
author = {Santos, JR and Park, J},
title = {MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891112},
issn = {2073-4409},
support = {n/a//Canada Research Chairs/ ; 202104PJT-462444-NSB-CEAB-275899/CAPMC/CIHR/Canada ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Nuclear Matrix-Associated Proteins/metabolism/genetics ; *Gene Expression Regulation ; *Nuclear Matrix/metabolism ; Animals ; RNA-Binding Proteins/metabolism/genetics ; },
abstract = {Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival. In addition to the revelation of its biological role, recent studies have reported MATR3's involvement in the context of various diseases, including neurodegenerative and neurodevelopmental diseases, as well as cancer. Moreover, sequencing studies of patients revealed a handful of disease-associated mutations in MATR3 linked to amyotrophic lateral sclerosis (ALS), which further elevated the gene's importance as a topic of study. In this review, we synthesize the current knowledge regarding the diverse functions of MATR3 in DNA- and RNA-related processes, as well as its involvement in various diseases, with a particular emphasis on ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Nuclear Matrix-Associated Proteins/metabolism/genetics
*Gene Expression Regulation
*Nuclear Matrix/metabolism
Animals
RNA-Binding Proteins/metabolism/genetics

@article {pmid38891099,
year = {2024},
author = {Hernan-Godoy, M and Rouaux, C},
title = {From Environment to Gene Expression: Epigenetic Methylations and One-Carbon Metabolism in Amyotrophic Lateral Sclerosis.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891099},
issn = {2073-4409},
support = {ANR-21-CE16-0024//Agence Nationale de la Recherche/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Epigenesis, Genetic ; *DNA Methylation/genetics ; *Carbon/metabolism ; Animals ; },
abstract = {The etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is complex and considered multifactorial. The majority of ALS cases are sporadic, but familial cases also exist. Estimates of heritability range from 8% to 61%, indicating that additional factors beyond genetics likely contribute to ALS. Numerous environmental factors are considered, which may add up and synergize throughout an individual's lifetime building its unique exposome. One level of integration between genetic and environmental factors is epigenetics, which results in alterations in gene expression without modification of the genome sequence. Methylation reactions, targeting DNA or histones, represent a large proportion of epigenetic regulations and strongly depend on the availability of methyl donors provided by the ubiquitous one-carbon (1C) metabolism. Thus, understanding the interplay between exposome, 1C metabolism, and epigenetic modifications will likely contribute to elucidating the mechanisms underlying altered gene expression related to ALS and to developing targeted therapeutic interventions. Here, we review evidence for 1C metabolism alterations and epigenetic methylation dysregulations in ALS, with a focus on the impairments reported in neural tissues, and discuss these environmentally driven mechanisms as the consequences of cumulative exposome or late environmental hits, but also as the possible result of early developmental defects.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
*Epigenesis, Genetic
*DNA Methylation/genetics
*Carbon/metabolism
Animals

@article {pmid38891059,
year = {2024},
author = {Dashtmian, AR and Darvishi, FB and Arnold, WD},
title = {Chronological and Biological Aging in Amyotrophic Lateral Sclerosis and the Potential of Senolytic Therapies.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891059},
issn = {2073-4409},
support = {1R01AG067758, R01AG078129, and R01AG067758-02S2//national institute of health/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; *Aging/pathology ; Senotherapeutics/pharmacology/therapeutic use ; Animals ; Cellular Senescence ; Mitochondria/metabolism/pathology ; DNA Damage ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a group of sporadic and genetic neurodegenerative disorders that result in losses of upper and lower motor neurons. Treatment of ALS is limited, and survival is 2-5 years after disease onset. While ALS can occur in younger individuals, the risk significantly increases with advancing age. Notably, both sporadic and genetic forms of ALS share pathophysiological features overlapping hallmarks of aging including genome instability/DNA damage, mitochondrial dysfunction, inflammation, proteostasis, and cellular senescence. This review explores chronological and biological aging in the context of ALS onset and progression. Age-related muscle weakness and motor unit loss mirror aspects of ALS pathology and coincide with peak ALS incidence, suggesting a potential link between aging and disease development. Hallmarks of biological aging, including DNA damage, mitochondrial dysfunction, and cellular senescence, are implicated in both aging and ALS, offering insights into shared mechanisms underlying disease pathogenesis. Furthermore, senescence-associated secretory phenotype and senolytic treatments emerge as promising avenues for ALS intervention, with the potential to mitigate neuroinflammation and modify disease progression.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy
Humans
*Aging/pathology
Senotherapeutics/pharmacology/therapeutic use
Animals
Cellular Senescence
Mitochondria/metabolism/pathology
DNA Damage

@article {pmid38891021,
year = {2024},
author = {Nguyen, L},
title = {Updates on Disease Mechanisms and Therapeutics for Amyotrophic Lateral Sclerosis.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891021},
issn = {2073-4409},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/drug therapy ; Animals ; C9orf72 Protein/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a motor neuron disease. In ALS, upper and lower motor neurons in the brain and spinal cord progressively degenerate during the course of the disease, leading to the loss of the voluntary movement of the arms and legs. Since its first description in 1869 by a French neurologist Jean-Martin Charcot, the scientific discoveries on ALS have increased our understanding of ALS genetics, pathology and mechanisms and provided novel therapeutic strategies. The goal of this review article is to provide a comprehensive summary of the recent findings on ALS mechanisms and related therapeutic strategies to the scientific audience. Several highlighted ALS research topics discussed in this article include the 2023 FDA approved drug for SOD1 ALS, the updated C9orf72 GGGGCC repeat-expansion-related mechanisms and therapeutic targets, TDP-43-mediated cryptic splicing and disease markers and diagnostic and therapeutic options offered by these recent discoveries.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/drug therapy
Animals
C9orf72 Protein/genetics

@article {pmid38891002,
year = {2024},
author = {Genchi, G and Lauria, G and Catalano, A and Carocci, A and Sinicropi, MS},
title = {Neuroprotective Effects of Curcumin in Neurodegenerative Diseases.},
journal = {Foods (Basel, Switzerland)},
volume = {13},
number = {11},
pages = {},
pmid = {38891002},
issn = {2304-8158},
abstract = {Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and prion disease, due to its potent anti-inflammatory, antioxidant potential, anticancerous, immunomodulatory, neuroprotective, antiproliferative, and antibacterial activities. Traditionally, curcumin has been used for medicinal and dietary purposes in Asia, India, and China. However, low water solubility, poor stability in the blood, high rate of metabolism, limited bioavailability, and little capability to cross the blood-brain barrier (BBB) have limited the clinical application of curcumin, despite the important pharmacological activities of this drug. A variety of nanocarriers, including liposomes, micelles, dendrimers, cubosome nanoparticles, polymer nanoparticles, and solid lipid nanoparticles have been developed with great success to effectively deliver the active drug to brain cells. Functionalization on the surface of nanoparticles with brain-specific ligands makes them target-specific, which should significantly improve bioavailability and reduce harmful effects. The aim of this review is to summarize the studies on curcumin and/or nanoparticles containing curcumin in the most common neurodegenerative diseases, highlighting the high neuroprotective potential of this nutraceutical.},
}

@article {pmid38889636,
year = {2024},
author = {Alkhazaali-Ali, Z and Sahab-Negah, S and Boroumand, AR and Tavakol-Afshari, J},
title = {MicroRNA (miRNA) as a biomarker for diagnosis, prognosis, and therapeutics molecules in neurodegenerative disease.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {177},
number = {},
pages = {116899},
doi = {10.1016/j.biopha.2024.116899},
pmid = {38889636},
issn = {1950-6007},
abstract = {Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.},
}

@article {pmid38889403,
year = {2024},
author = {Zhu, Y and Wang, F and Xia, Y and Wang, L and Lin, H and Zhong, T and Wang, X},
title = {Research progress on astrocyte-derived extracellular vesicles in the pathogenesis and treatment of neurodegenerative diseases.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {38889403},
issn = {2191-0200},
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles - both advantageous and disadvantageous in the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed.},
}

@article {pmid38883980,
year = {2024},
author = {Azam, HMH and Rößling, RI and Geithe, C and Khan, MM and Dinter, F and Hanack, K and Prüß, H and Husse, B and Roggenbuck, D and Schierack, P and Rödiger, S},
title = {MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.},
journal = {Frontiers in molecular neuroscience},
volume = {17},
number = {},
pages = {1386735},
pmid = {38883980},
issn = {1662-5099},
abstract = {Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.},
}

@article {pmid38878554,
year = {2024},
author = {Mincic, AM and Antal, M and Filip, L and Miere, D},
title = {Modulation of gut microbiome in the treatment of neurodegenerative diseases: A systematic review.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {43},
number = {7},
pages = {1832-1849},
doi = {10.1016/j.clnu.2024.05.036},
pmid = {38878554},
issn = {1532-1983},
abstract = {BACKGROUND AND AIMS: Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

METHODS: PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.

RESULTS: Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.

CONCLUSIONS: The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.},
}

@article {pmid38877004,
year = {2024},
author = {Costa, RG and Conceição, A and Matos, CA and Nóbrega, C},
title = {The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease.},
journal = {Cell death & disease},
volume = {15},
number = {6},
pages = {415},
pmid = {38877004},
issn = {2041-4889},
mesh = {Humans ; *Ataxin-2/metabolism/genetics ; *Peptides/metabolism/genetics ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Spinocerebellar Ataxias/metabolism/genetics/pathology ; },
abstract = {A CAG repeat sequence in the ATXN2 gene encodes a polyglutamine (polyQ) tract within the ataxin-2 (ATXN2) protein, showcasing a complex landscape of functions that have been progressively unveiled over recent decades. Despite significant progresses in the field, a comprehensive overview of the mechanisms governed by ATXN2 remains elusive. This multifaceted protein emerges as a key player in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and the regulation of the circadian rhythm. The CAG overexpansion within the ATXN2 gene produces a protein with an extended poly(Q) tract, inducing consequential alterations in conformational dynamics which confer a toxic gain and/or partial loss of function. Although overexpanded ATXN2 is predominantly linked to spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also implicated in amyotrophic lateral sclerosis (ALS) and parkinsonism. While the molecular intricacies await full elucidation, SCA2 presents ATXN2-associated pathological features, encompassing autophagy impairment, RNA-mediated toxicity, heightened oxidative stress, and disruption of calcium homeostasis. Presently, SCA2 remains incurable, with patients reliant on symptomatic and supportive treatments. In the pursuit of therapeutic solutions, various studies have explored avenues ranging from pharmacological drugs to advanced therapies, including cell or gene-based approaches. These endeavours aim to address the root causes or counteract distinct pathological features of SCA2. This review is intended to provide an updated compendium of ATXN2 functions, delineate the associated pathological mechanisms, and present current perspectives on the development of innovative therapeutic strategies.},
}

Humans
*Ataxin-2/metabolism/genetics
*Peptides/metabolism/genetics
Animals
Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Spinocerebellar Ataxias/metabolism/genetics/pathology

@article {pmid38874845,
year = {2024},
author = {Birbaumer, N},
title = {"Your Thoughts are (were) Free!": Brain-Computer-Interfaces, Neurofeedback, Detection of Deception, and the Future of Mind-Reading.},
journal = {Applied psychophysiology and biofeedback},
volume = {},
number = {},
pages = {},
pmid = {38874845},
issn = {1573-3270},
abstract = {This review describes the historical developement and rationale of clinically relevant research on neurophysiological "mind reading" paradims: Brain- Computer-Interfaces, detection of deception, brain stimulation and neurofeedback and the clinical applications in drug resistant epilepsy, chronic stroke, and communication with paralyzed locked-in persons. The emphasis lies on completely locked-in patients with amyotrophic lateral sclerosis using non-invasive and invasive brain computer interfaces and neurofeedback to restore verbal communication with the social environment. In the second part of the article we argue that success and failure of neurophysiological "mind reading" paradigms may be explained with a motor theory of thinking and emotion in combination with learning theory. The ethical implications of brain computer interface and neurofeedback approaches, particularly for severe chronic paralysis and loss of communication diseases and decisions on hastened death and euthanasia are discussed.},
}

@article {pmid38871941,
year = {2024},
author = {Naik, B and Sasikumar, J and Das, SP},
title = {From Skin and Gut to the Brain: The Infectious Journey of the Human Commensal Fungus Malassezia and Its Neurological Consequences.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {38871941},
issn = {1559-1182},
support = {GIA/2019/000620/PRCGIA//Indian Council of Medical Research/ ; GIA/2019/000620/PRCGIA//Indian Council of Medical Research/ ; },
abstract = {The human mycobiome encompasses diverse communities of fungal organisms residing within the body and has emerged as a critical player in shaping health and disease. While extensive research has focused on the skin and gut mycobiome, recent investigations have pointed toward the potential role of fungal organisms in neurological disorders. Among those fungal organisms, the presence of the commensal fungus Malassezia in the brain has created curiosity because of its commensal nature and primary association with the human skin and gut. This budding yeast is responsible for several diseases, such as Seborrheic dermatitis, Atopic dermatitis, Pityriasis versicolor, Malassezia folliculitis, dandruff, and others. However recent findings surprisingly show the presence of Malassezia DNA in the brain and have been linked to diseases like Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. The exact role of Malassezia in these disorders is unknown, but its ability to infect human cells, travel through the bloodstream, cross the blood-brain barrier, and reside along with the lipid-rich neuronal cells are potential mechanisms responsible for pathogenesis. This also includes the induction of pro-inflammatory cytokines, disruption of the blood-brain barrier, gut-microbe interaction, and accumulation of metabolic changes in the brain environment. In this review, we discuss these key findings from studies linking Malassezia to neurological disorders, emphasizing the complex and multifaceted nature of these cases. Furthermore, we discuss potential mechanisms through which Malassezia might contribute to the development of neurological conditions. Future investigations will open up new avenues for our understanding of the fungal gut-brain axis and how it influences human behavior. Collaborative research efforts among microbiologists, neuroscientists, immunologists, and clinicians hold promise for unraveling the enigmatic connections between human commensal Malassezia and neurological disorders.},
}

@article {pmid38870925,
year = {2024},
author = {Hamdi, N and Ocab, O and Soliman, R and Ludolph, A and Anwar, W and Logroscino, G and Fahmy, N},
title = {Motor Neuron Disease Population-Based Registry in Egypt: Where Do We Stand?.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1159/000539468},
pmid = {38870925},
issn = {1423-0208},
abstract = {BACKGROUND: There is a growing body of evidence indicating that the worldwide distribution of ALS is far from uniform. This is evident through variations in the epidemiology, genetics, and phenotypical characteristics of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND) across different regions. However, comprehensive ALS epidemiological studies are still lacking in many parts of the world, especially in Africa. Therefore, we propose the establishment of a population-based register for ALS/MND in Egypt, an important part of Africa with a population of more than 100 millions of people.

SUMMARY: Given Egypt's distinctive social and demographic characteristics, it is highly recommended to employ specific, recently developed epidemiological techniques for assessing the prevalence and incidence of these diseases within the country. By utilizing these methods, we can gather invaluable data that will contribute to a deeper understanding of ALS and enable us to effectively address its impact on the population of Egypt.

KEY MESSAGES: Our goal with this pioneering ALS/MND population-based register in Egypt is to define the burden of ALS in this part of Africa and to increase the chances for this consanguineous population to get access to modern individualized genetic therapies. Additionally, we aspire to uncover potential environmental factors and gene-environment interactions that contribute to the development of ALS. This knowledge of MND individual and group risk in Egypt will not only open doors for interventions but also provide opportunities for future research and discovery.},
}

@article {pmid38869826,
year = {2024},
author = {Wang, H and Zeng, R},
title = {Aberrant protein aggregation in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38869826},
issn = {1432-1459},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease. As its pathological mechanisms are not well understood, there are no efficient therapeutics for it at present. While it is highly heterogenous both etiologically and clinically, it has a common salient hallmark, i.e., aberrant protein aggregation (APA). The upstream pathogenesis and the downstream effects of APA in ALS are sophisticated and the investigation of this pathology would be of consequence for understanding ALS. In this paper, the pathomechanism of APA in ALS and the candidate treatment strategies for it are discussed.},
}

@article {pmid38864944,
year = {2024},
author = {Wang, LY and Zhang, L and Bai, XY and Qiang, RR and Zhang, N and Hu, QQ and Cheng, JZ and Yang, YL and Xiang, Y},
title = {The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.},
journal = {Neurochemical research},
volume = {},
number = {},
pages = {},
pmid = {38864944},
issn = {1573-6903},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.},
}

@article {pmid38859699,
year = {2024},
author = {Finsterer, J and Strobl, W},
title = {Gastrointestinal involvement in neuromuscular disorders.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.16650},
pmid = {38859699},
issn = {1440-1746},
abstract = {Although not often discussed, many of the neuromuscular disorders (NMDs) affect the gastrointestinal tract (GIT). Depending on the type of NMD, the prevalence of GIT involvement ranges from <5% (e.g. hereditary neuropathies, myofibrillar myopathies) to 100% (e.g. MNGIE, OPMD). Particularly in NMDs with multisystem affection, involvement of the GIT can dominate the clinical presentation or at least make up a significant part of the clinical picture. The most prominent representatives of NMDs with multisystem involvement are the mitochondrial disorders (MIDs) and the myotonic dystrophies. The best known syndromic MIDs with GIT involvement are MNGIE, MELAS, Leigh, and Pearson syndromes. Among neuropathies, GIT involvement is most commonly found in ALS and GBS. GIT involvement may also be a feature of myasthenia. The clinical manifestations of GIT involvement are diverse and can affect the entire GIT, from the teeth to the rectum, including the liver and pancreas. The most well-known clinical manifestations of GIT involvement are dysphagia, nausea, vomiting, reflux, hollow organ dysmotility, hepatopathy, diabetes, diarrhea, constipation, and fecal incontinence. Even if treatment can usually only be symptomatic, the therapeutic options are diverse, are often effective, and can significantly and beneficially influence the course of the underlying NMD.},
}

@article {pmid38531340,
year = {2024},
author = {Lee, KH and Kim, MH and Kim, J and Nam, HJ},
title = {Acupuncture for Tinnitus: A Scoping Review of Clinical Studies.},
journal = {Complementary medicine research},
volume = {31},
number = {3},
pages = {292-301},
doi = {10.1159/000538236},
pmid = {38531340},
issn = {2504-2106},
mesh = {Humans ; *Acupuncture Therapy/methods ; *Tinnitus/therapy ; Randomized Controlled Trials as Topic ; Acupuncture Points ; },
abstract = {BACKGROUND: Acupuncture treatment for tinnitus has received attention owing to its potential as an alternative to conventional treatment modalities. We conducted a scoping review to identify detailed information on acupuncture treatment methods used in clinical studies and to provide useful information for practitioners, patients, and researchers.

METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA), and the China National Knowledge Infrastructure (CNKI) were searched from their inception to December 2023. This review included single-arm trials, open-label randomized controlled trials (RCTs), and double-blind RCTs using needle-type acupuncture to treat tinnitus in English, Chinese, and Korean. We investigated basic and detailed information on the acupuncture treatment methods, assessment methods, and study outcomes. Network analysis was also conducted to evaluate the centrality between acupoints in the double-blind RCTs.

RESULTS: We included 106 articles. There were 11 single-arm trials, 90 open-label RCTs, and 5 double-blind RCTs. Most (89.6%) of these studies were conducted in China. Manual acupuncture was the most common type of acupuncture in treatment group. A total of 119 acupuncture points were used 1,138 times. The most frequently used acupoints were local points around the ear (TE17, GB2, SI19, and TE21). Both local and distant acupoints were used simultaneously in these studies. The treatment duration of 20-39 days, 10 to 19 sessions of treatment, the mean acupuncture duration of 30 min, needle diameter of 0.30 mm × 40 mm, and needling depth over 30 mm and less than 50 mm were confirmed as the most common.

CONCLUSION: These study outcomes will enable future acupuncture studies on tinnitus to perform more effective and standardized acupuncture treatments in selecting acupoints and procedures. Furthermore, the study has implications for informing clinicians and students about more impactful acupuncture strategies for addressing tinnitus.

UNLABELLED: Die Anwendung von Akupunktur bei Tinnitus erhält seit einiger Zeit Aufmerksamkeit als potenzielle Alternative zu konventionellen Behandlungsmodalitäten. Wir führten einen Scoping-Review durch, um detaillierte Informationen zu den in klinischen Studien angewandten Akupunktur-Behandlungsmethoden zu sammeln und nützliche Informationen für Praktiker, Patienten und Forscher bereitzustellen.MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA) und die China National Knowledge Infrastructure (CNKI) wurden von ihrem jeweiligen Beginn bis Dezember 2023 durchsucht. In diese Übersichtsarbeit wurden einarmige Studien, offene, randomisierte, kontrollierte Studien (RCTs) sowie doppelt verblindete RCTs zu Nadel-Akupunktur zur Behandlung von Tinnitus in englischer, chinesischer und koreanischer Sprache einbezogen. Wir untersuchten grundlegende und detaillierte Informationen zu den Akupunktur-Behandlungsmethoden, Untersuchungsmethoden und Studienergebnissen. Außerdem wurden Netzwerkanalysen zur Beurteilung der Zentralität zwischen Akupunkten in den doppelt verblindeten RCTs durchgeführt.106 Artikel wurden eingeschlossen. Sie behandelten 11 einarmige Studien, 90 offene RCTs und 5 doppelt verblindete RCTs. Die meisten (89,6%) dieser Studien waren in China durchgeführt worden. Manuelle Akupunktur war die häufigste Form der Akupunktur in den Behandlungsgruppen. 119 Akupunkturpunkte wurden insgesamt 1’138 Mal verwendet. Die am häufigsten verwendeten Akupunkte waren lokale Punkte im Bereich des Ohrs (TE17, GB2, SI19 und TE21). Jedoch wurden in den Studien lokale und entfernte Akupunkte gleichzeitig angewendet. Außerdem wurde festgestellt, dass die Behandlungsdauer am häufigsten 20 bis 39 Tage betrug, die Zahl der Sitzungen 10 bis 19, die mittlere Akupunkturdauer 30 Minuten, die Nadelgröße 0.30 mm × 40 mm und die Einstichtiefe zwischen 30 mm und weniger als 50 mm.Diese Studienergebnisse bieten eine Grundlage für künftige Studien zu Akupunktur bei Tinnitus, um durch die Auswahl der Akupunkte und Verfahren wirksamere und standardisierte Akupunkturbehandlungen durchzuführen. Darüber hinaus hat die Studie Implikationen für die Aufklärung von Praktikern und Schülern über wirkungsvollere Akupunkturstrategien zur Behandlung von Tinnitus.},
}

Humans
*Acupuncture Therapy/methods
*Tinnitus/therapy
Randomized Controlled Trials as Topic
Acupuncture Points

@article {pmid38037913,
year = {2024},
author = {Zhong, G and Wang, X and Li, J and Xie, Z and Wu, Q and Chen, J and Wang, Y and Chen, Z and Cao, X and Li, T and Liu, J and Wang, Q},
title = {Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.},
journal = {Current neuropharmacology},
volume = {22},
number = {10},
pages = {1650-1671},
pmid = {38037913},
issn = {1875-6190},
support = {81973918, 82274616//National Natural Science Foundation of China/ ; 2019KSYS005//Key laboratory project of colleges and universities in Guangdong Province/ ; 2020A0505100052//Guangdong province science and technology plan international cooperation project/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Copper/metabolism ; Animals ; Biological Products/therapeutic use/pharmacology ; Homeostasis/drug effects ; Chelating Agents/therapeutic use/pharmacology ; },
abstract = {Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
*Copper/metabolism
Animals
Biological Products/therapeutic use/pharmacology
Homeostasis/drug effects
Chelating Agents/therapeutic use/pharmacology

@article {pmid38856890,
year = {2024},
author = {Tripathi, S and Bhawana, },
title = {Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.},
journal = {Neurochemical research},
volume = {},
number = {},
pages = {},
pmid = {38856890},
issn = {1573-6903},
abstract = {Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.},
}

@article {pmid38856793,
year = {2024},
author = {Kumari, S and Kamiya, A and Karnik, SS and Rohilla, S and Dubey, SK and Taliyan, R},
title = {Novel Gene Therapy Approaches for Targeting Neurodegenerative Disorders: Focusing on Delivering Neurotrophic Genes.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {38856793},
issn = {1559-1182},
abstract = {Neurodegenerative illnesses (NDDs) like Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, spinal muscular atrophy, and Huntington's disease have demonstrated considerable potential for gene therapy as a viable therapeutic intervention. NDDs are marked by the decline of neurons, resulting in changes in both behavior and pathology within the body. Strikingly, only symptomatic management is available without a cure for the NDDs. There is an unmet need for a permanent therapeutic approach. Many studies have been going on to target the newer therapeutic molecular targets for NDDs including gene-based therapy. Gene therapy has the potential to provide therapeutic benefits to a large number of patients with NDDs by offering mechanisms including neuroprotection, neuro-restoration, and rectification of pathogenic pathways. Gene therapy is a medical approach that aims to modify the biological characteristics of living cells by controlling the expression of specific genes in certain neurological disorders. Despite being the most complex and well-protected organ in the human body, there is clinical evidence to show that it is possible to specifically target the central nervous system (CNS). This provides hope for the prospective application of gene therapy in treating NDDs in the future. There are several advanced techniques available for using viral or non-viral vectors to deliver the therapeutic gene to the afflicted region. Neurotrophic factors (NTF) in the brain are crucial for the development, differentiation, and survival of neurons in the CNS, making them important in the context of various neurological illnesses. Gene delivery of NTF has the potential to be used as a therapeutic approach for the treatment of neurological problems in the brain. This review primarily focuses on the methodologies employed for delivering the genes of different NTFs to treat neurological disorders. These techniques are currently being explored as a viable therapeutic approach for neurodegenerative diseases. The article exclusively addresses gene delivery approaches and does not cover additional therapy strategies for NDDs. Gene therapy offers a promising alternative treatment for NDDs by stimulating neuronal growth instead of solely relying on symptom relief from drugs and their associated adverse effects. It can serve as a long-lasting and advantageous treatment choice for the management of NDDs. The likelihood of developing NDDs increases with age as a result of neuronal degradation in the brain. Gene therapy is an optimal approach for promoting neuronal growth through the introduction of nerve growth factor genes.},
}

@article {pmid38560897,
year = {2024},
author = {Minatoguchi, S and Fujita, Y and Niizuma, K and Tominaga, T and Yamashita, T and Abe, K and Dezawa, M},
title = {Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment.},
journal = {Stem cells translational medicine},
volume = {13},
number = {6},
pages = {532-545},
doi = {10.1093/stcltm/szae018},
pmid = {38560897},
issn = {2157-6580},
support = {//New Energy and Industrial Technology Development Organization/ ; //Japan Agency for Medical Research and Development/ ; //Ministry of Education, Culture, Sports, Science and Technology/ ; //Japan Society for the Promotion of Science/ ; //SENSHIN Medical Research Foundation/ ; //Life Science Institute Inc/ ; },
mesh = {Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; Mesenchymal Stem Cell Transplantation/methods ; Immunosuppressive Agents/pharmacology/therapeutic use ; HLA Antigens/metabolism ; Cell Differentiation ; Animals ; Histocompatibility Testing/methods ; },
abstract = {The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.},
}

Humans
*Mesenchymal Stem Cells/cytology/metabolism
Mesenchymal Stem Cell Transplantation/methods
Immunosuppressive Agents/pharmacology/therapeutic use
HLA Antigens/metabolism
Cell Differentiation
Animals
Histocompatibility Testing/methods

@article {pmid38855322,
year = {2024},
author = {Tsekrekou, M and Giannakou, M and Papanikolopoulou, K and Skretas, G},
title = {Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.},
journal = {Frontiers in molecular biosciences},
volume = {11},
number = {},
pages = {1383453},
pmid = {38855322},
issn = {2296-889X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.},
}

@article {pmid38848023,
year = {2024},
author = {Fabi, JP},
title = {The connection between gut microbiota and its metabolites with neurodegenerative diseases in humans.},
journal = {Metabolic brain disease},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11011-024-01369-w},
pmid = {38848023},
issn = {1573-7365},
support = {2013/07914-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 307842/2022-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota.},
}

@article {pmid38846716,
year = {2024},
author = {Bradford, D and Rodgers, KE},
title = {Advancements and challenges in amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1401706},
pmid = {38846716},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) continues to pose a significant challenge due to the disease complexity and heterogeneous manifestations. Despite recent drug approvals, there remains a critical need for the development of more effective therapies. This review explores the underlying mechanisms involved; including neuroinflammation, glutamate mediated excitotoxicity, mitochondrial dysfunction, and hypermetabolism, and how researchers are trying to develop novel drugs to target these pathways. While progress has been made, the unmet need of ALS patients highlights the urgency for continued research and resource allocation in the pursuit of effective treatments.},
}

@article {pmid38845026,
year = {2024},
author = {Kettunen, P and Koistinaho, J and Rolova, T},
title = {Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {152},
pmid = {38845026},
issn = {1742-2094},
support = {334525//Research Council of Finland/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Central Nervous System Infections ; Animals ; },
abstract = {Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.},
}

Humans
*Neurodegenerative Diseases/pathology
*Central Nervous System Infections
Animals

@article {pmid38844617,
year = {2024},
author = {Tyr, A and Heldring, N and Zilg, B},
title = {Examining the use of alternative light sources in medico-legal assessments of blunt-force trauma: a systematic review.},
journal = {International journal of legal medicine},
volume = {},
number = {},
pages = {},
pmid = {38844617},
issn = {1437-1596},
abstract = {The ability to analyze blunt-force trauma is crucial for deciphering valuable clues concerning mechanisms of injury and as evidence for medico-legal investigations. The use of alternate light sources (ALS) has been studied over the past decade, and is proposed to outperform conventional white light (CWL) during bruise assessments. In response to the growing interest of the technology worldwide, a systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to address the ability of ALS to detect and visualize bruising. From an initial 4055 records identified, ten studies met the eligibly criteria and were selected for this review. Evaluation also included a novel framework, referred to as SPICOT, to further systematically assess both scientific evidence and risk of bias in forensic literature. Analysis reveals that narrowband wavelengths within in the infrared or ultraviolet spectral ranges do not significantly outperform CWL in visualizing or detecting bruising. However, wavelengths within the visible spectrum, particularly 415 nm combined with longpass or bandpass yellow filters, are more effective. However, the majority of selected studies only address the sensitivity of ALS, and therefore, results may only be considered valid when the location of a bruise is known. Further investigation is required to understand the specificity of ALS, in particular how the use of topical cosmetic products, previous wounds/scar-tissue, tattoos, moles and freckles may affect detection. The ethical concern regarding the interpretation of enhanced visualized trauma should also be considered in prospect discussions prior to implementing ALS into routine practice. Nevertheless, this review finds that narrowband ALS within the visible spectrum demonstrates potential for improved injury documentation, outperforming CWL in the detection and visualization of bruising.},
}

@article {pmid38831349,
year = {2024},
author = {López-Carbonero, JI and García-Toledo, I and Fernández-Hernández, L and Bascuñana, P and Gil-Moreno, MJ and Matías-Guiu, JA and Corrochano, S},
title = {In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.},
journal = {Translational neurodegeneration},
volume = {13},
number = {1},
pages = {29},
pmid = {38831349},
issn = {2047-9158},
support = {2022-5A/BMD-24221//Consejería de Educación, Juventud y Deporte, Comunidad de Madrid/ ; PDI2020-1153-70RB-100/AEI/10.13039/501100011033//Ministerio de Ciencia e Innovación/ ; CM23/00094//Instituto de Salud Carlos III/ ; INT20/00079//Instituto de Salud Carlos III/ ; INT23/00017//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; *TDP-43 Proteinopathies/diagnosis/metabolism/genetics ; *Biomarkers/analysis/metabolism ; *DNA-Binding Proteins/metabolism ; Brain/metabolism/pathology ; },
abstract = {TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer's disease, Huntington's disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.},
}

Humans
*TDP-43 Proteinopathies/diagnosis/metabolism/genetics
*Biomarkers/analysis/metabolism
*DNA-Binding Proteins/metabolism
Brain/metabolism/pathology

@article {pmid38712849,
year = {2024},
author = {Ludolph, AC and Corcia, P and Desnuelle, C and Heiman-Patterson, T and Mora, JS and Mansfield, CD and Couratier, P},
title = {Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice.},
journal = {Muscle & nerve},
volume = {70},
number = {1},
pages = {36-41},
doi = {10.1002/mus.28101},
pmid = {38712849},
issn = {1097-4598},
support = {//AB Science/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; *Research Design ; Severity of Illness Index ; Outcome Assessment, Health Care/standards ; Clinical Trials as Topic/methods ; Disease Progression ; },
abstract = {The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post-onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post-onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post-onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Humans
*Research Design
Severity of Illness Index
Outcome Assessment, Health Care/standards
Clinical Trials as Topic/methods
Disease Progression

@article {pmid37016529,
year = {2024},
author = {Adam, H and Gopinath, SCB and Arshad, MKM and Adam, T and Subramaniam, S and Hashim, U},
title = {An Update on Parkinson's Disease and its Neurodegenerative Counterparts.},
journal = {Current medicinal chemistry},
volume = {31},
number = {19},
pages = {2770-2787},
pmid = {37016529},
issn = {1875-533X},
mesh = {Humans ; *Parkinson Disease/metabolism/pathology/diagnosis ; Neurodegenerative Diseases/metabolism/pathology ; alpha-Synuclein/metabolism ; Multiple System Atrophy/metabolism/diagnosis/pathology ; Animals ; },
abstract = {INTRODUCTION: Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases.

BACKGROUND: Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism.

METHOD: Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers.

RESULTS: Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations.

CONCLUSION: We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.},
}

Humans
*Parkinson Disease/metabolism/pathology/diagnosis
Neurodegenerative Diseases/metabolism/pathology
alpha-Synuclein/metabolism
Multiple System Atrophy/metabolism/diagnosis/pathology
Animals

@article {pmid38829511,
year = {2024},
author = {Jiang, S and Xu, R},
title = {The Current Potential Pathogenesis of Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {38829511},
issn = {1559-1182},
support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202210002//Health and Family Planning Commission of Jiangxi Province/ ; 202310119//Health and Family Planning Commission of Jiangxi Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.},
}

@article {pmid38822985,
year = {2024},
author = {Faysal, M and Dehbia, Z and Zehravi, M and Sweilam, SH and Haque, MA and Kumar, KP and Chakole, RD and Shelke, SP and Sirikonda, S and Nafady, MH and Khan, SL and Nainu, F and Ahmad, I and Emran, TB},
title = {Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.},
journal = {Neurochemical research},
volume = {},
number = {},
pages = {},
pmid = {38822985},
issn = {1573-6903},
abstract = {Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca[2+] stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.},
}

@article {pmid38822416,
year = {2024},
author = {Yadav, S and Deepika, and Moar, K and Kumar, A and Khola, N and Pant, A and Kakde, GS and Maurya, PK},
title = {Reconsidering red blood cells as the diagnostic potential for neurodegenerative disorders.},
journal = {Biology of the cell},
volume = {},
number = {},
pages = {e2400019},
doi = {10.1111/boc.202400019},
pmid = {38822416},
issn = {1768-322X},
support = {//Council of Scientific and Industrial Research (CSIR), Government of India/ ; //University Grant Commission (UGC)/ ; HSCIT-3946//Haryana State Council for Science, Innovation, and Technology/ ; //Central University of Haryana, Mahendergarh/ ; //Indian Council of Medical Research (ICMR), Government of India/ ; },
abstract = {BACKGROUND: Red blood cells (RBCs) are usually considered simple cells and transporters of gases to tissues.

HYPOTHESIS: However, recent research has suggested that RBCs may have diagnostic potential in major neurodegenerative disorders (NDDs).

RESULTS: This review summarizes the current knowledge on changes in RBC in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other NDDs. It discusses the deposition of neuronal proteins like amyloid-β, tau, and α-synuclein, polyamines, changes in the proteins of RBCs like band-3, membrane transporter proteins, heat shock proteins, oxidative stress biomarkers, and altered metabolic pathways in RBCs during neurodegeneration. It also highlights the comparison of RBC diagnostic markers to other in-market diagnoses and discusses the challenges in utilizing RBCs as diagnostic tools, such as the need for standardized protocols and further validation studies.

SIGNIFICANCE STATEMENT: The evidence suggests that RBCs have diagnostic potential in neurodegenerative disorders, and this study can pave the foundation for further research which may lead to the development of novel diagnostic approaches and treatments.},
}

@article {pmid38821351,
year = {2024},
author = {Pocock, J and Vasilopoulou, F and Svensson, E and Cosker, K},
title = {Microglia and TREM2.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110020},
doi = {10.1016/j.neuropharm.2024.110020},
pmid = {38821351},
issn = {1873-7064},
abstract = {TREM2 is a membrane receptor solely expressed on microglia in normal brain. In this review we outline recent advances in TREM2 biology and its implications for microglial function, with particular emphasis on findings from iPSC-derived microglia (iMG) expressing TREM2 loss-of-function mutations. Alterations in receptor proximal and distal signalling underlie TREM2 risk variants linked to neurodegenerative disease, principally NH-linked FTD, and late-onset AD, but emerging data suggest roles for TREM2 in PD, MS and ALS. TREM2 downstream functions include phagocytosis of myelin debris, amyloid beta peptides, and phosphatidylserine-expressing cells (resulting from damage or stress). Microglial survival, migration, DAMP signalling, inflammasome activation, and intercellular signalling including tau spreading via exosomes, as well as roles for sTREM2 ain protection and as a biomarker are discussed. The role of TREM2 in metabolic homeostasis, and immunometabolic switching are discussed regarding microglial responses to damage and protection. The use of iPSC models to investigate the role of TREM2 in AD, PD, MS, ALS, and other neurodegenerative diseases could prove invaluable due to their ability to recapitulate human pathology, allowing a full understanding of TREM2 and microglial involvement in the underlying disease mechanisms and progression.},
}

@article {pmid38819491,
year = {2024},
author = {Juarez, D and Handal-Silva, A and Morán-Perales, JL and Torres-Cifuentes, DM and Flores, G and Treviño, S and Moreno-Rodriguez, A and Guevara, J and Diaz, A},
title = {New insights into sodium phenylbutyrate as a pharmacotherapeutic option for neurological disorders.},
journal = {Synapse (New York, N.Y.)},
volume = {78},
number = {4},
pages = {e22301},
doi = {10.1002/syn.22301},
pmid = {38819491},
issn = {1098-2396},
support = {IN214117//PAPITT-UNAM/ ; DIFA-NAT24-G//Vicerrectoría de Investigación y Estudios de Posgrado, Benemérita Universidad Autónoma de Puebla/ ; TEMS-NAT24-G//Vicerrectoría de Investigación y Estudios de Posgrado, Benemérita Universidad Autónoma de Puebla/ ; },
mesh = {Humans ; *Phenylbutyrates/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; },
abstract = {Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.},
}

Humans
*Phenylbutyrates/therapeutic use/pharmacology
Animals
*Nervous System Diseases/drug therapy/metabolism

@article {pmid38818523,
year = {2024},
author = {Shen, J and Wang, X and Wang, M and Zhang, H},
title = {Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.},
journal = {Frontiers in physiology},
volume = {15},
number = {},
pages = {1337442},
doi = {10.3389/fphys.2024.1337442},
pmid = {38818523},
issn = {1664-042X},
abstract = {Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune system disorders. Prominent neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Insulin resistance refers to the inability of the peripheral and central tissues of the body to respond to insulin and effectively regulate blood sugar levels. Insulin resistance has been observed in various neurodegenerative diseases and has been suggested to induce the occurrence, development, and exacerbation of neurodegenerative diseases. Furthermore, an increasing number of studies have suggested that reversing insulin resistance may be a critical intervention for the treatment of neurodegenerative diseases. Among the numerous measures available to improve insulin sensitivity, exercise is a widely accepted strategy due to its convenience, affordability, and significant impact on increasing insulin sensitivity. This review examines the association between neurodegenerative diseases and insulin resistance and highlights the molecular mechanisms by which exercise can reverse insulin resistance under these conditions. The focus was on regulating insulin resistance through exercise and providing practical ideas and suggestions for future research focused on exercise-induced insulin sensitivity in the context of neurodegenerative diseases.},
}

@article {pmid38816479,
year = {2024},
author = {Mathis, S and Beauvais, D and Duval, F and Solé, G and Le Masson, G},
title = {The various forms of hereditary motor neuron disorders and their historical descriptions.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38816479},
issn = {1432-1459},
abstract = {Motor neuron disorders comprise a clinically and pathologically heterogeneous group of neurologic diseases characterized by progressive degeneration of motor neurons (including both sporadic and hereditary diseases), affecting the upper motor neurons, lower motor neurons, or both. Hereditary motor neuron disorders themselves represent a vast and heterogeneous group, with numerous clinical and genetic overlaps that can be a source of error. This narrative review aims at providing an overview of the main types of inherited motor neuron disorders by recounting the stages in their historical descriptions. For practical purposes, this review of the literature sets out their various clinical characteristics and updates the list of all the genes involved in the various forms of inherited motor neuron disorders, including spinal muscular atrophy, familial amyotrophic lateral sclerosis, hereditary spastic paraplegia, distal hereditary motor neuropathies/neuronopathies, Kennedy's disease, riboflavin transporter deficiencies, VCPopathy and the neurogenic scapuloperoneal syndrome.},
}

@article {pmid38812793,
year = {2024},
author = {Jadhav, SP},
title = {MicroRNAs in microglia: deciphering their role in neurodegenerative diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1391537},
pmid = {38812793},
issn = {1662-5102},
abstract = {This review presents a comprehensive analysis of the role of microRNAs in microglia and their implications in the pathogenesis of neurodegenerative diseases. Microglia, as the resident immune cells of the central nervous system (CNS), are pivotal in maintaining neural homeostasis and responding to pathological changes. Recent studies have highlighted the significance of miRNAs, small non-coding RNA molecules, in regulating microglial functions. In neurodegenerative diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), dysregulated miRNA expression in microglia contributes to disease progression through various mechanisms such regulation of gene expression, as modulation of cytokine response and phagocytosis. This review synthesizes current knowledge on how miRNAs influence microglial activation, cytokine production, and phagocytic activity. Specific miRNAs, such as miR-155, are explored for their roles in modulating microglial responses in the context of neuroinflammation and neurodegeneration. The study also discusses the impact of miRNA dysregulation on the transition of microglia from a neuroprotective to a neurotoxic phenotype, a critical aspect in the progression of neurodegenerative diseases.},
}

@article {pmid38811997,
year = {2024},
author = {Huang, M and Liu, YU and Yao, X and Qin, D and Su, H},
title = {Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.},
journal = {Translational neurodegeneration},
volume = {13},
number = {1},
pages = {28},
pmid = {38811997},
issn = {2047-9158},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/epidemiology/diagnosis ; Humans ; *Superoxide Dismutase-1/genetics ; Mutation/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and limited post-diagnosis life expectancy. Although primarily sporadic, familial ALS (fALS) cases suggest a genetic basis. This review focuses on SOD1, the first gene found to be associated with fALS, which has been more recently confirmed by genome sequencing. While informative, databases such as ALSoD and STRENGTH exhibit regional biases. Through a systematic global examination of SOD1 mutations from 1993 to 2023, we found different geographic distributions and clinical presentations. Even though different SOD1 variants are expressed at different protein levels and have different half-lives and dismutase activities, these alterations lead to loss of function that is not consistently correlated with disease severity. Gain of function of toxic aggregates of SOD1 resulting from mutated SOD1 has emerged as one of the key contributors to ALS. Therapeutic interventions specifically targeting toxic gain of function of mutant SOD1, including RNA interference and antibodies, show promise, but a cure remains elusive. This review provides a comprehensive perspective on SOD1-associated ALS and describes molecular features and the complex genetic landscape of SOD1, highlighting its importance in determining diverse clinical manifestations observed in ALS patients and emphasizing the need for personalized therapeutic strategies.},
}

*Amyotrophic Lateral Sclerosis/genetics/therapy/epidemiology/diagnosis
Humans
*Superoxide Dismutase-1/genetics
Mutation/genetics

@article {pmid38807021,
year = {2024},
author = {Rahimian, S and Najafi, H and Webber, CA and Jalali, H},
title = {Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.},
journal = {Neurochemical research},
volume = {},
number = {},
pages = {},
pmid = {38807021},
issn = {1573-6903},
abstract = {Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.},
}

@article {pmid38805053,
year = {2024},
author = {Bjelica, B and Bartels, MB and Hesebeck-Brinckmann, J and Petri, S},
title = {Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38805053},
issn = {1432-1459},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients' quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice.},
}

@article {pmid38802184,
year = {2024},
author = {Vucic, S and de Carvalho, M and Bashford, J and Alix, JJP},
title = {Contribution of neurophysiology to the diagnosis and monitoring of ALS.},
journal = {International review of neurobiology},
volume = {176},
number = {},
pages = {87-118},
doi = {10.1016/bs.irn.2024.04.001},
pmid = {38802184},
issn = {2162-5514},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation/methods ; *Electromyography/methods ; *Neurophysiology/methods ; Disease Progression ; Motor Cortex/physiopathology ; },
abstract = {This chapter describes the role of neurophysiological techniques in diagnosing and monitoring amyotrophic lateral sclerosis (ALS). Despite many advances, electromyography (EMG) remains a keystone investigation from which to build support for a diagnosis of ALS, demonstrating the pathophysiological processes of motor unit hyperexcitability, denervation and reinnervation. We consider development of the different diagnostic criteria and the role of EMG therein. While not formally recognised by established diagnostic criteria, we discuss the pioneering studies that have demonstrated the diagnostic potential of transcranial magnetic stimulation (TMS) of the motor cortex and highlight the growing evidence for TMS in the diagnostic process. Finally, accurately monitoring disease progression is crucial for the successful implementation of clinical trials. Neurophysiological measures of disease state have been incorporated into clinical trials for over 20 years and we review prominent techniques for assessing disease progression.},
}

*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Humans
*Transcranial Magnetic Stimulation/methods
*Electromyography/methods
*Neurophysiology/methods
Disease Progression
Motor Cortex/physiopathology

@article {pmid38802183,
year = {2024},
author = {Moll, T and Harvey, C and Alhathli, E and Gornall, S and O'Brien, D and Cooper-Knock, J},
title = {Non-coding genome contribution to ALS.},
journal = {International review of neurobiology},
volume = {176},
number = {},
pages = {75-86},
doi = {10.1016/bs.irn.2024.04.002},
pmid = {38802183},
issn = {2162-5514},
mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; Animals ; Genetic Predisposition to Disease/genetics ; },
abstract = {The majority of amyotrophic lateral sclerosis (ALS) is caused by a complex gene-environment interaction. Despite high estimates of heritability, the genetic basis of disease in the majority of ALS patients are unknown. This limits the development of targeted genetic therapies which require an understanding of patient-specific genetic drivers. There is good evidence that the majority of these missing genetic risk factors are likely to be found within the non-coding genome. However, a major challenge in the discovery of non-coding risk variants is determining which variants are functional in which specific CNS cell type. We summarise current discoveries of ALS-associated genetic drivers within the non-coding genome and we make the case that improved cell-specific annotation of genomic function is required to advance this field, particularly via single-cell epigenetic profiling and spatial transcriptomics. We highlight the example of TBK1 where an apparent paradox exists between pathogenic coding variants which cause loss of protein function, and protective non-coding variants which cause reduced gene expression; the paradox is resolved when it is understood that the non-coding variants are acting primarily via change in gene expression within microglia, and the effect of coding variants is most prominent in neurons. We propose that cell-specific functional annotation of ALS-associated genetic variants will accelerate discovery of the genetic architecture underpinning disease in the vast majority of patients.},
}

*Amyotrophic Lateral Sclerosis/genetics
Humans
Animals
Genetic Predisposition to Disease/genetics

@article {pmid38802182,
year = {2024},
author = {Al-Chalabi, A and Andrews, J and Farhan, S},
title = {Recent advances in the genetics of familial and sporadic ALS.},
journal = {International review of neurobiology},
volume = {176},
number = {},
pages = {49-74},
doi = {10.1016/bs.irn.2024.04.007},
pmid = {38802182},
issn = {2162-5514},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genetic Predisposition to Disease/genetics ; },
abstract = {ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age. Genetic susceptibility factors also contribute to risk, and the heritability of ALS is between 40% and 60%. The genetic variants influencing ALS risk include single base changes, repeat expansions, copy number variants, and others. Here we review what is known of the genetic landscape and architecture of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Genetic Predisposition to Disease/genetics

@article {pmid38802181,
year = {2024},
author = {De Cock, L and Bercier, V and Van Den Bosch, L},
title = {New developments in pre-clinical models of ALS to guide translation.},
journal = {International review of neurobiology},
volume = {176},
number = {},
pages = {477-524},
doi = {10.1016/bs.irn.2024.04.008},
pmid = {38802181},
issn = {2162-5514},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/physiopathology/therapy ; Animals ; *Disease Models, Animal ; Humans ; Translational Research, Biomedical/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder in which selective death of motor neurons leads to muscle weakness and paralysis. Most research has focused on understanding and treating monogenic familial forms, most frequently caused by mutations in SOD1, FUS, TARDBP and C9orf72, although ALS is mostly sporadic and without a clear genetic cause. Rodent models have been developed to study monogenic ALS, but despite numerous pre-clinical studies and clinical trials, few disease-modifying therapies are available. ALS is a heterogeneous disease with complex underlying mechanisms where several genes and molecular pathways appear to play a role. One reason for the high failure rate of clinical translation from the current models could be oversimplification in pre-clinical studies. Here, we review advances in pre-clinical models to better capture the heterogeneous nature of ALS and discuss the value of novel model systems to guide translation and aid in the development of precision medicine.},
}

*Amyotrophic Lateral Sclerosis/genetics/physiopathology/therapy
Animals
*Disease Models, Animal
Humans
Translational Research, Biomedical/methods