43,894 results match your criteria lateral sclerosis


Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases.

Biomed Pharmacother 2021 Apr 14;139:111551. Epub 2021 Apr 14.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China. Electronic address:

The central nervous system (CNS) is a vital part of the human nervous system, and the incidence of CNS disease is increasing year by year, which has become a major public health problem and a prominent social problem. At present, the drugs most commonly used in the clinic are receptor regulators, and neurotransmitter inhibitors, but they are accompanied by serious side effects. Therefore, the identification of new drugs and treatment strategies for CNS disease has been a research hotspot in the medical field. Read More

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Combinatrial treatment of anti-High mobility group box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury.

Neurosci Res 2021 Apr 14. Epub 2021 Apr 14.

Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, we here examined combinatorial treatment of anti-HMGB1 mAb and epothilone B (Epo B), which has been reported to promote axon regeneration. Read More

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Cognitive and behavioural impairment in amyotrophic lateral sclerosis: A landmark of the disease? A mini review of longitudinal studies.

Neurosci Lett 2021 Apr 15;754:135898. Epub 2021 Apr 15.

3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease marked by progressive loss of motor abilities. Approximately half of patents with ALS experience cognitive (ALSci) or behavioural impairment (ALSbi) during the course of the disease, with a small percentage developing overt frontotemporal dementia (FTD). ALSci and/or ALSbi can occur simultaneously with motor neuron degeneration or develop in advanced stages of the disease, but it can even precede motor involvement in some cases, namely in ALS patients meeting criteria for FTD. Read More

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Targeting Adenosine Receptors in Neurological Diseases.

Cell Reprogram 2021 Apr;23(2):57-72

Department of Clinical Nutrition, NUR International University, Lahore, Pakistan.

Adenosine plays a significant role in neurotransmission process by controlling the blood pressure, while adenosine triphosphate (ATP) acts as a neuromodulator and neurotransmitter and by activation of P2 receptors, regulates the contractility of the heart. Adenosine signaling is essential in the process of regeneration by regulating proliferation, differentiation, and apoptosis of stem cells. In this review, we have selected neurological disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy) with clinical trials using antagonists and epigenetic tools targeting adenosine receptor as a therapeutic approach in the treatment of these disorders. Read More

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Fucoidan: a promising agent for brain injury and neurodegenerative disease intervention.

Food Funct 2021 Apr 16. Epub 2021 Apr 16.

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China. and Institute of Neuroscience, Zhengzhou University, Zhengzhou, 450052, Henan, China.

Brain injury and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are urgent medical problems, which severely threaten the life quality of patients and their carers. However, there are currently no effective therapies. Fucoidan is a natural compound found in brown algae and some animals, which has multiple biological and pharmacological activities, such as antioxidant, anti-tumor, anti-coagulant, anti-thrombotic, immunoregulatory, anti-viral, and anti-inflammatory effects. Read More

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Slow progression of amyotrophic lateral sclerosis in a Chinese patient carrying SOD1 p.S135T mutation.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Apr 16:1-3. Epub 2021 Apr 16.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China and.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Most patients die of respiratory failure within 3 years of onset. In this study, we reported a female Chinese ALS patient with SOD1 c. Read More

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Amyotrophic lateral sclerosis caregiver burden and patients' quality of life during COVID-19 pandemic.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Apr 16:1-3. Epub 2021 Apr 16.

"Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy.

To assess patients Quality of life (QoL) and the burden of their caregivers during Covid-19 pandemic and specifically the impact of two-month lockdown period. : In April 2020, a total of 60 patients and 59 caregivers were administered by phone scales assessing patients' QoL (McGill QoL Questionnaire), general health status (EQ-5D-5L), and caregiver burden (Zarit Burden Interview). The administration was repeated one month after the end of lockdown measures, with the addition of a qualitative questionnaire (COVID-QoL Questionnaire) exploring family reorganization and personal perception of lock down. Read More

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Recruitment of population-based controls for ALS cases from the National ALS Registry.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Apr 16:1-7. Epub 2021 Apr 16.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, and.

In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases ( = 280). Read More

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Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling.

Neurotherapeutics 2021 Apr 15. Epub 2021 Apr 15.

Department of Neurology, University Hospital Regensburg, Regensburg, Germany.

Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor-Receptor Type II) specific LNA-antisense oligonucleotide ("locked nucleotide acid"-"NVP-13"), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. Read More

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Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment.

Mol Neurobiol 2021 Apr 15. Epub 2021 Apr 15.

ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.

Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. Read More

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The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors.

J Neuropathol Exp Neurol 2021 Apr 16. Epub 2021 Apr 16.

From the Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA (BCC, Y-WC); Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA (BCC); and Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA (BCC, EBL).

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins. This protein aggregation suggests that abnormal proteostasis contributes to aging-related neurodegeneration. A better fundamental understanding of proteins that regulate proteostasis may provide insight into the pathophysiology of neurodegenerative disease and may perhaps reveal novel therapeutic opportunities. Read More

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Altered perivascular fibroblast activity precedes ALS disease onset.

Nat Med 2021 Apr 15;27(4):640-646. Epub 2021 Apr 15.

Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.

Apart from well-defined factors in neuronal cells, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia and blood vessels. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Read More

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Primary lateral sclerosis: diagnostic contribution of brain [F]FDG PET/CT.

Rev Esp Med Nucl Imagen Mol 2021 Apr 12. Epub 2021 Apr 12.

Servicio de Medicina Nuclear, Hospital Universitario Central de Asturias, Oviedo, Asturias, España.

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Identification of hub molecules of FUS-ALS by Bayesian gene regulatory network analysis of iPSC model: iBRN.

Neurobiol Dis 2021 Apr 12:105364. Epub 2021 Apr 12.

Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address:

Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of amyotrophic lateral sclerosis (ALS). Mutated FUS causes accumulation of DNA damage and cytosolic stress granule (SG) formation, thereby motor neuron (MN) death. However, key molecular aetiology remains unclear. Read More

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A Helicase Unwinds Hexanucleotide Repeat RNA G-Quadruplexes and Facilitates Repeat-Associated Non-AUG Translation.

J Am Chem Soc 2021 Apr 15. Epub 2021 Apr 15.

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United States.

The expansion of a hexanucleotide repeat GGGGCC (G4C2) in the gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 expansion leads to repeat-associated non-AUG (RAN) translation and the production of toxic dipeptide repeat (DPR) proteins, but the mechanisms of RAN translation remain enigmatic. Here, we report that the RNA helicase DHX36 is a robust positive regulator of RAN translation. Read More

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O-GlcNAcylation of TDP-43 suppresses proteinopathies and promotes TDP-43's mRNA splicing activity.

EMBO Rep 2021 Apr 15:e51649. Epub 2021 Apr 15.

Hubei Key Laboratory of Cell Homeostasis, RNA Institute, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.

Pathological TDP-43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP); however, how TDP-43 aggregation and function are regulated remain poorly understood. Here, we show that O-GlcNAc transferase OGT-mediated O-GlcNAcylation of TDP-43 suppresses ALS-associated proteinopathies and promotes TDP-43's splicing function. Biochemical and cell-based assays indicate that OGT's catalytic activity suppresses TDP-43 aggregation and hyperphosphorylation, whereas abolishment of TDP-43 O-GlcNAcylation impairs its RNA splicing activity. Read More

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Mesenchymal Stem Cells for Neurological Disorders.

Adv Sci (Weinh) 2021 Apr 24;8(7):2002944. Epub 2021 Feb 24.

NeuroRepair Department Mossakowski Medical Research Centre PAS Warsaw 02-106 Poland.

Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell-based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Read More

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Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Front Neurol 2021 29;12:613834. Epub 2021 Mar 29.

Advanced Imaging and Radiomics Center, Neuroradiology Department, IRCCS Mondino Foundation, Pavia, Italy.

Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Read More

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Destination Amyotrophic Lateral Sclerosis.

Front Neurol 2021 29;12:596006. Epub 2021 Mar 29.

Epigenes Australia Pty Ltd., Melbourne, VIC, Australia.

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. Read More

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Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases.

Genome Med 2021 Apr 14;13(1):59. Epub 2021 Apr 14.

Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, Antwerp, Belgium.

Knowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Read More

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Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene.

Neuroreport 2021 Apr 12. Epub 2021 Apr 12.

Department of Applied Biology Advanced Insect Research Promotion Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama Kansai Gakken Laboratory, Kankyo Eisei Yakuhin Co. Ltd., Kyoto, Japan.

Mutations in the factor-induced-gene 4 (FIG 4) gene are associated with multiple disorders, including Charcot-Marie-Tooth disease (CMT), epilepsy with polymicrogyria, Yunis-Varón syndrome and amyotrophic lateral sclerosis. The wide spectrum of disorders associated with FIG 4 may be related to the dysregulated epigenetics. Using Gene Expression Omnibus, we found that HDAC1 binds to the FIG 4 gene locus in the genome of human CD4+ T cells. Read More

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The cumulative incidence of dysphagia and dysphagia-free survival in persons diagnosed with Amyotrophic Lateral Sclerosis.

Muscle Nerve 2021 Apr 13. Epub 2021 Apr 13.

Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Clinical and Translational Sciences Institute Tufts Medical Center, Boston, Ma.

Introduction/aims: Dysphagia worsens mortality and quality of life for persons diagnosed with amyotrophic lateral sclerosis (ALS), yet our understanding of its incidence and timing remains limited. We sought to estimate dysphagia incidence and dysphagia-free survival over time.

Methods: Using data from the Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT), we compared characteristics of persons with and without dysphagia upon study entry. Read More

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Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene.

Neuroreport 2021 May;32(7):562-568

Department of Applied Biology.

Mutations in the factor-induced-gene 4 (FIG 4) gene are associated with multiple disorders, including Charcot-Marie-Tooth disease (CMT), epilepsy with polymicrogyria, Yunis-Varón syndrome and amyotrophic lateral sclerosis. The wide spectrum of disorders associated with FIG 4 may be related to the dysregulated epigenetics. Using Gene Expression Omnibus, we found that HDAC1 binds to the FIG 4 gene locus in the genome of human CD4+ T cells. Read More

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[ decoction produces antidepressant-like effects sirt1-p53 signaling pathway].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Mar;41(3):399-405

Key Laboratory of Mental Health of Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Provincial Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Objective: To investigate the mechanism of the antidepressant-like effects of decoction (CGD).

Objective: Chaihu Guizhi decoction at the daily dose of 17 g/kg and solvent vehicle were administered by gavage in 12 and 14 male C57BL/6J mice for 7 consecutive days, respectively. Forced swimming test (FST), elevated plus maze (EPM) test, open field test (OFT) and novelty-suppressed feeding test (NSF) were performed to assess the depression- and anxiety-like behaviors and motor ability of the mice. Read More

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Stapedial Reflex: A Possible Novel Biomarker of Early Bulbar Involvement in Amyotrophic Lateral Sclerosis Patients.

Audiol Neurootol 2021 Apr 13:1-8. Epub 2021 Apr 13.

ENT Unit, Department of Surgical Sciences, University of Turin, Turin, Italy.

Background And Aim: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder, characterized by limb and bulbar muscle wasting and weakness. 30% of patients present a bulbar onset, while 70% a spinal outbreak, although most of them develop bulbar impairment later on. Due to the lack of an early biomarker of bulbar involvement, we chose to evaluate the role of stapedial reflex (SR) in order to predict preclinical bulbar impairment in ALS. Read More

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Simvastatin accelerated motoneurons death in SOD1 mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles.

Cell Death Dis 2021 Apr 12;12(4):392. Epub 2021 Apr 12.

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, P.R. China.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by motoneuron loss, for which there is currently no effective treatment. Statins, as inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are used as drugs for treatment for a variety of disease such as ischemic diseases, neurodegenerative diseases, cancer, and inflammation. However, our previous evidence has demonstrated that simvastatin leads to cytotoxicity in NSC34-hSOD1 cells by aggravating the impairment of autophagic flux, but the role of simvastatin in ALS model remains elusive. Read More

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Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis.

BMC Neurol 2021 Apr 12;21(1):157. Epub 2021 Apr 12.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue 1095, 430030, Wuhan, Hubei, PR China.

Background: ALS patients have changed peripheral immunity. It is unknown whether peripheral immunity is related to cognitive dysfunction in ALS patients.

Objective: To explore the relationship between the peripheral blood lymphocyte subsets and the cognitive status in ALS patients. Read More

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Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons.

Neurobiol Dis 2021 Apr 13;155:105366. Epub 2021 Apr 13.

Neuronal Signaling Unit, Experimental Medicine Department, Universitat de Lleida-IRBLleida, Rovira Roure, 80, 25198, Lleida, Spain.. Electronic address:

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder caused by loss of the Survival Motor Neuron 1 gene (SMN1). Due to this depletion of the survival motor neuron (SMN) protein, the disease is characterized by the degeneration of spinal cord motoneurons (MNs), progressive muscular atrophy, and weakness. Nevertheless, the ultimate cellular and molecular mechanisms leading to cell loss in SMN-reduced MNs are only partially known. Read More

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The cannabinoid system and microglia in health and disease.

Neuropharmacology 2021 Apr 9:108555. Epub 2021 Apr 9.

Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, UNSW Sydney, NSW, 2052, Australia. Electronic address:

Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostatic microglia have a unique molecular signature. Read More

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Characterization of Adult Patients With SMA Treated in US Hospital Settings: A Natural History Study in the Premier Healthcare Database.

J Neuromuscul Dis 2021 Apr 2. Epub 2021 Apr 2.

Biogen, Cambridge, MA, USA.

Background: Spinal muscular atrophy (SMA) is a rare genetic disease characterized by progressive muscular weakness and atrophy resulting from motor neuron degeneration. Limited information is available on disease progression among older SMA patients, particularly adults.

Objective: This study sought to characterize the natural history of SMA among adult patients in US hospital settings through the assessment of symptoms, complications, costs, and healthcare resource utilization (HRU) over 3 years before the availability of disease-modifying therapies. Read More

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