39,173 results match your criteria Primary Lateral Sclerosis


Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease.

Phytomedicine 2022 Jun 16;104:154281. Epub 2022 Jun 16.

Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China. Electronic address:

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L. Read More

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Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson's disease.

Phytomedicine 2022 Jun 15;104:154250. Epub 2022 Jun 15.

Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan. Electronic address:

Background: Parkinson's disease (PD) is a neurodegenerative disorder involving the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Cellular clearance mechanisms, including the autophagy-lysosome pathway, are commonly affected in the pathogenesis of PD. The lysosomal Ca channel mucolipin TRP channel 1 (TRPML1) is one of the most important proteins involved in the regulation of autophagy. Read More

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Does epilepsy contribute to the clinical phenotype of C9orf72 mutation in fronto-temporal dementia?

Epilepsy Behav 2022 Jun 22;133:108783. Epub 2022 Jun 22.

Institute of Neurology, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy; Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

C9orf72 mutation is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Recently, several reports of patients with FTD who carried the C9orf72 mutation and also manifested epilepsy have been published, since seizures occur in FTD at a higher rate than in the general population, the possible association between epilepsy and C9orf72 mutation remains to be clarified. In the attempt to understand whether epilepsy contributes to the phenotype of the C9orf72 mutation, we compared epilepsy occurrence in patients with FTD who carried the C9orf72 mutation and those who did not. Read More

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Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis.

Stem Cell Reports 2022 Jun 9. Epub 2022 Jun 9.

College of Medicine and Health, University of Exeter, Exeter EX1 2LU, UK; Living Systems Institute, University of Exeter, Exeter EX4 4QD, UK. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons (MNs). There are no effective treatments and patients usually die within 2-5 years of diagnosis. Emerging commonalities between familial and sporadic cases of this complex multifactorial disorder include disruption to RNA processing and cytoplasmic inclusion bodies containing TDP-43 and/or FUS protein aggregates. Read More

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Retromer dysfunction in amyotrophic lateral sclerosis.

Proc Natl Acad Sci U S A 2022 Jun 24;119(26):e2118755119. Epub 2022 Jun 24.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032.

Retromer is a heteropentameric complex that plays a specialized role in endosomal protein sorting and trafficking. Here, we report a reduction in the retromer proteins-vacuolar protein sorting 35 (VPS35), VPS26A, and VPS29-in patients with amyotrophic lateral sclerosis (ALS) and in the ALS model provided by transgenic (Tg) mice expressing the mutant superoxide dismutase-1 G93A. These changes are accompanied by a reduction of levels of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA1, a proxy of retromer function, in spinal cords from Tg SOD1 mice. Read More

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Triggers for Referral to Specialized Palliative Care in Advanced Neurologic and Neurosurgical Conditions: A Systematic Review.

Neurol Clin Pract 2022 Jun;12(3):190-202

Department of Clinical Neurological Sciences (KM, KK, MEJ, TEG), Western University, London, Ontario, Canada; and Library Services (AEI), London Health Sciences Centre, Ontario, Canada.

Background And Objectives: To systematically review the literature for the most suitable trigger criteria for referral to specialist palliative care services in life-limiting and life-threatening neurologic and neurosurgical conditions.

Methods: Literature searches were conducted in Ovid MEDLINE and EMBASE (1990-December 2020). To be included, studies must have trigger/referral criteria clearly outlined, a ≥75% nononcology neurosciences population, and consensus or guidelines documents regarding palliative neurosciences or trigger/referral criteria. Read More

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A pathologically confirmed case of combined amyotrophic lateral sclerosis with C9orf72 mutation and multiple system atrophy.

Neuropathology 2022 Jun 23. Epub 2022 Jun 23.

London Neurodegenerative Diseases Brain Bank and Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Hexanucleotide repeat expansions in C9orf72 account for a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. There have been occasional reported cases associated with this expansion but also additional extrapyramidal clinical features. However, only very rarely has there been pathological confirmation of a parkinsonian syndrome associated with a C9orf72 repeat expansion. Read More

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Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity.

Molecules 2022 Jun 16;27(12). Epub 2022 Jun 16.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia.

Amyotrophic lateral sclerosis (ALS) is a severe adult motor neuron disease that causes progressive neuromuscular atrophy, muscle wasting, weakness, and depressive-like symptoms. Our previous research suggests that mercury levels are directly associated with ALS progression. MeHg+-induced ALS is characterised by oligodendrocyte destruction, myelin basic protein (MBP) depletion, and white matter degeneration, leading to demyelination and motor neuron death. Read More

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Optineurin Deficiency and Insufficiency Lead to Higher Microglial TDP-43 Protein Levels.

Int J Mol Sci 2022 Jun 19;23(12). Epub 2022 Jun 19.

Laboratory of Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia.

Mutations in optineurin, a ubiquitin-binding adaptor protein, cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease of motor neurons linked to chronic inflammation and protein aggregation. The majority of ALS patients, including those carrying the optineurin mutations, exhibit cytoplasmic mislocalization, ubiquitination, and aggregation of nuclear TAR DNA-binding protein 43 kDa (TDP-43). To address the crosstalk between optineurin and TDP-43, we generated optineurin knockout (KO) neuronal and microglial cell lines using the CRISPR/Cas9 approach. Read More

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Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson's Disease through an Inflammatory Response.

Int J Mol Sci 2022 Jun 10;23(12). Epub 2022 Jun 10.

Department of Physiology, College of Korean Medicine, Kyung Hee University, 26-6 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02453, Korea.

Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson's disease (PD). Read More

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Nonalcoholic Fatty Liver Disease in Patients with Inherited and Sporadic Motor Neuron Degeneration.

Genes (Basel) 2022 May 24;13(6). Epub 2022 May 24.

Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.

We describe evidence of fatty liver disease in patients with forms of motor neuron degeneration with both genetic and sporadic etiology compared to controls. A group of 13 patients with motor neuron disease underwent liver imaging and laboratory analysis. The cohort included five patients with hereditary spastic paraplegia, four with sporadic amyotrophic lateral sclerosis (ALS), three with familial ALS, and one with primary lateral sclerosis. Read More

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Molecular Pathogenesis and New Therapeutic Dimensions for Spinal Muscular Atrophy.

Biology (Basel) 2022 Jun 10;11(6). Epub 2022 Jun 10.

Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), 28001 Madrid, Spain.

The condition known as 5q spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the and genes. It is one of the most common pediatric recessive genetic diseases, and it represents the most common cause of hereditary infant mortality. After decades of intensive basic and clinical research efforts, and improvements in the standard of care, successful therapeutic milestones have been developed, delaying the progression of 5q SMA and increasing patient survival. Read More

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Comprehensive In Silico Analysis of Retrotransposon Insertions within the Genes Involved in Spinal Muscular Atrophy.

Biology (Basel) 2022 May 27;11(6). Epub 2022 May 27.

Laboratory of Cytogenomics and Animal Genomics (CAG), Department of Genetics and Biotechnology (DGB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.

Transposable elements (TEs) are interspersed repetitive and mobile DNA sequences within the genome. Better tools for evaluating TE-derived sequences have provided insights into the contribution of TEs to human development and disease. Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that is caused by deletions or mutations in the () gene but retention of its nearly perfect orthologue . Read More

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Role of Seipin in Human Diseases and Experimental Animal Models.

Biomolecules 2022 Jun 17;12(6). Epub 2022 Jun 17.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 () gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and -associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. Read More

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New Insights into the Neurodegeneration Mechanisms Underlying Riboflavin Transporter Deficiency (RTD): Involvement of Energy Dysmetabolism and Cytoskeletal Derangement.

Biomedicines 2022 Jun 6;10(6). Epub 2022 Jun 6.

Department of Science, LIME, University Roma Tre, 00165 Rome, Italy.

Riboflavin transporter deficiency (RTD) is a rare genetic disorder characterized by motor, sensory and cranial neuropathy. This childhood-onset neurodegenerative disease is caused by biallelic pathogenic variants in either or genes, resulting in insufficient supply of riboflavin (vitamin B2) and consequent impairment of flavoprotein-dependent metabolic pathways. Current therapy, empirically based high-dose riboflavin supplementation, ameliorates the progression of the disease, even though response to treatment is variable and partial. Read More

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N-cystaminylbiguanide MC001 prevents neuron cell death and alleviates motor deficits in the MPTP-model of Parkinson's disease.

Neurosci Lett 2022 Jun 20:136751. Epub 2022 Jun 20.

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School Shenzhen, 518055, China. Electronic address:

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN), which is highly associated with oxidative stress. Antioxidants are therefore considered as potential therapies in PD treatment. In this study, we examined the neuroprotective effect of a cysteamine-based biguanide N-cystaminylbiguanide (MC001) in the MPTP mouse model of PD. Read More

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Brain Codelivery of Temozolomide and Cisplatin for Combinatorial Glioblastoma Chemotherapy.

Adv Mater 2022 Jun 23:e2203958. Epub 2022 Jun 23.

Henan-Macquarie Uni Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China.

Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Temozolomide (TMZ) and cisplatin (CDDP) based combinational therapy shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood-brain-barrier (BBB) penetration, poor targeting of GBM tissue/cells and systemic side effect which hinder its efficacy in GBM therapy. Read More

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Imaging Neurodegenerative Metabolism in Amyotrophic Lateral Sclerosis with Hyperpolarized [1-C]pyruvate MRI.

Tomography 2022 Jun 14;8(3):1570-1577. Epub 2022 Jun 14.

Center of Functionally Integrative Neuroscience, Aarhus University, 8200 Aarhus, Denmark.

The cause of amyotrophic lateral sclerosis (ALS) is still unknown, and consequently, early diagnosis of the disease can be difficult and effective treatment is lacking. The pathology of ALS seems to involve specific disturbances in carbohydrate metabolism, which may be diagnostic and therapeutic targets. Magnetic resonance imaging (MRI) with hyperpolarized [1-C]pyruvate is emerging as a technology for the evaluation of pathway-specific changes in the brain's metabolism. Read More

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[Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon].

Rev Med Chil 2021 Dec;149(12):1751-1764

Laboratorio de Neurología y Neurofisiología Traslacional, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Read More

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December 2021

[Genetics of frontotemporal dementia].

Authors:
Y A L Pijnenburg

Tijdschr Psychiatr 2022 ;64(5):306-311

Background: Frontotemporal dementia (FTD) is a neurodegenerative disorder leading to dementia. Because of predominant behavioural and emotional features it often presents to the psychiatrist. AIM: Provide an overview of the genetic background of FTD with recommendations for the clinician. Read More

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Disease Modifying Therapies for the Management of Children with Spinal Muscular Atrophy (5q SMA): An Update on the Emerging Evidence.

Drug Des Devel Ther 2022 16;16:1865-1883. Epub 2022 Jun 16.

Department of Neuropediatrics, Astrid Lindgren Children´s Hospital, Karolinska University Hospital, Stockholm, Sweden.

SMA (5q SMA) is an autosomal recessive neuromuscular disease with an estimated incidence of approximately 1 in 11,000 live births, characterized by progressive degeneration and loss of α-motor neurons in the spinal cord and brain stem, resulting in progressive muscle weakness. The disease spectrum is wide, from a serious congenital to a mild adult-onset disease. SMA is caused by biallelic mutations in the gene and disease severity is modified primarily by copy number. Read More

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Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway.

Authors:
Harry T Orr

Cerebellum 2022 Jun 23. Epub 2022 Jun 23.

Institute of Translational Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA.

This is a summary of the virtual presentation given at the 2021 meeting of the Society for Research on the Cerebellum and Ataxias, https://www.meetings.be/SRCA2021/ , where the therapeutic potential of the CCK-CCK1R pathway for treating diseases involving Purkinje cell degeneration was presented. Read More

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Movement Disorder and Neurotoxicity Induced by Chronic Exposure to Microcystin-LR in Mice.

Mol Neurobiol 2022 Jun 22. Epub 2022 Jun 22.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.

Microcystins are produced by some species of cyanobacteria, which are hazardous materials to the environment and human beings. It has been demonstrated that microcystin-LR (MC-LR) could disrupt the blood-brain barrier and cause learning and memory deficits, but the neurotoxicity of MC-LR on motor function remains unclear. In this study, the mice were exposed to MC-LR dissolved in drinking water at doses of 1, 7. Read More

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Association between DNA methylation variability and self-reported exposure to heavy metals.

Sci Rep 2022 Jun 22;12(1):10582. Epub 2022 Jun 22.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.

Individuals encounter varying environmental exposures throughout their lifetimes. Some exposures such as smoking are readily observed and have high personal recall; others are more indirect or sporadic and might only be inferred from long occupational histories or lifestyles. We evaluated the utility of using lifetime-long self-reported exposures for identifying differential methylation in an amyotrophic lateral sclerosis cases-control cohort of 855 individuals. Read More

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Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4.

Nature 2022 Jun 22. Epub 2022 Jun 22.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Amyotrophic lateral sclerosis (ALS) is a heterogenous neurodegenerative disorder that affects motor neurons and voluntary muscle control. ALS heterogeneity includes the age of manifestation, the rate of progression and the anatomical sites of symptom onset. Disease-causing mutations in specific genes have been identified and define different subtypes of ALS. Read More

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The role of nutrition on Parkinson's disease: a systematic review.

Nutr Neurosci 2022 Jun 22:1-24. Epub 2022 Jun 22.

King Abdulaziz University, Department of occupational therapy. Jeddah, Makkah, Saudi Arabia.

Background: Parkinson's disease (PD) in elderly patients is the second most prevalent neurodegenerative disease. The pathogenesis of PD is associated with dopaminergic neuron degeneration of the substantia nigra in the basal ganglia, causing classic motor symptoms. Oxidative stress, mitochondrial dysfunction, and neuroinflammation have been identified as possible pathways in laboratory investigations. Read More

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Investigating key factors underlying neurodegeneration linked to alpha-synuclein spread.

Neuropathol Appl Neurobiol 2022 Jun 21:e12829. Epub 2022 Jun 21.

Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Objectives: It has long been considered that accumulation of pathological alpha-synuclein (aSyn) leads to synaptic/neuronal loss which then results in behavioural and cognitive dysfunction. To investigate this claim, we investigated effects downstream of aSyn preformed fibrils (PFF) and 6-hydroxydopamine (6-OHDA), because aSyn PFFs induce spreading/accumulation of aSyn, and 6-OHDA rapidly causes local neuronal loss.

Materials And Methods: We injected mouse aSyn PFFs into the medial forebrain bundle (MFB) of Sprague-Dawley rats. Read More

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Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases.

Cell Mol Life Sci 2022 Jun 21;79(7):374. Epub 2022 Jun 21.

Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, Neurology Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Myostatin is a negative regulator of skeletal muscle growth secreted by skeletal myocytes. In the past years, myostatin inhibition sparked interest among the scientific community for its potential to enhance muscle growth and to reduce, or even prevent, muscle atrophy. These characteristics make it a promising target for the treatment of muscle atrophy in motor neuron diseases, namely, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), which are rare neurological diseases, whereby the degeneration of motor neurons leads to progressive muscle loss and paralysis. Read More

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Clinical and Electrophysiological Findings in C9ORF72 ALS.

Muscle Nerve 2022 Jun 21. Epub 2022 Jun 21.

Department of Neurology, Mayo Clinic, Rochester, MN.

Introduction/aims: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder of motor neurons in which the cause is mostly unknown. Early identification of genetic ALS cases, of which C9ORF72 (C9ALS) is the most frequent, can have important implications for evaluation, prognosis, and therapeutics. Here, we aimed to characterize the clinical and electrophysiological hallmarks of C9ALS and investigate differences from C9ORF72 negative ALS (non-C9ALS). Read More

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Amyotrophic lateral sclerosis in social media: Content analysis of YouTube videos.

Health Informatics J 2022 Apr-Jun;28(2):14604582221105999

Department of Nursing, 34961Gangneung-Wonju National University, Wonju-si, South Korea.

The purpose of this study is to analyze the characteristics, content, and quality of information available on YouTube regarding amyotrophic lateral sclerosis (ALS), and explore the search results and number of views and quality of the videos. A search was performed on YouTube on 10 June 2020, using the search term ''Lou Gehrig's disease" in the Korean language, and the first 100 videos were targeted for analysis. General characteristics (e. Read More

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