24,676 results match your criteria Amyotrophic Lateral Sclerosis


Safety, Tolerability, and Pharmacodynamics of Intrathecal Injection of Recombinant Human HGF (KP-100) in Subjects With Amyotrophic Lateral Sclerosis: A Phase I Trial.

J Clin Pharmacol 2018 Dec 11. Epub 2018 Dec 11.

Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Hepatocyte growth factor is an endogenous pleiotropic factor shown to act as a potent neuroprotectant against disease progression in animal models of amyotrophic lateral sclerosis, which is a devastating, adult-onset motor neuron disease. To evaluate the safety, tolerability, and pharmacokinetics of recombinant 5-residue-deleted human hepatocyte growth factor (KP-100) injected intrathecally through an implantable catheter connected to a subcutaneous port, we conducted a first-in-human phase I trial of intrathecal KP-100 in 15 Japanese patients with amyotrophic lateral sclerosis. The regimen was a single injection of 3 escalating doses (0. Read More

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December 2018
1 Read

Rare variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

Transl Neurodegener 2018 4;7:31. Epub 2018 Dec 4.

1Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008 China.

Background: The TANK-Binding Kinase 1 () gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the genetic contribution of in a Chinese cohort.

Methods: A total of 270 cases with ALS, FTD, or their combination were recruited into this study. Read More

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December 2018

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients.

Front Neurol 2018 26;9:971. Epub 2018 Nov 26.

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

To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis. 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13. Read More

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November 2018

NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?

Noncoding RNA Res 2018 Dec 15;3(4):243-252. Epub 2018 Nov 15.

Medicines Discovery Institute, School of Biosciences, Cardiff University, Park Place, Cardiff, CF10 3AT, United Kingdom.

Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experimental evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the CNS in health and disease. Read More

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December 2018

Long non coding RNAs and ALS: Still much to do.

Noncoding RNA Res 2018 Dec 15;3(4):226-231. Epub 2018 Nov 15.

Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy.

Alterations in RNA metabolism play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. The literature has described, so far, a small number of long non coding RNAs (lncRNAs) associated to ALS demonstrating that how there is still much to do to identify and understand their role in ALS. This class of RNAs may offer numerous starting points for new investigations about pathogenic mechanism involved in ALS disease. Read More

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December 2018

Non-coding RNA in -related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction.

Noncoding RNA Res 2018 Dec 10;3(4):178-187. Epub 2018 Sep 10.

Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

A hexanucleotide repeat expansion in the first intron/promoter region of is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both sense and antisense transcripts exist at the locus but the function of the antisense lncRNA is unknown. RNA toxicity of the transcribed repeat expansion has been implicated in the pathogenesis of -related ALS/FTD, not only through direct sequestration of important RNA binding proteins but also indirectly through non-ATG dependent translation into dipeptide repeats. Read More

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December 2018

Triple Stimulation Technique in Amyotrophic Lateral Sclerosis.

J Clin Neurophysiol 2018 Dec 7. Epub 2018 Dec 7.

Department of Neurology, Peking Union Medical College Hospital, Beijing, China.

Purpose: To identify upper motor neuron (UMN) dysfunction using the triple stimulation technique (TST) in amyotrophic lateral sclerosis (ALS).

Methods: Fifty ALS and 42 non-ALS patients were examined clinically, using conventional transcranial magnetic stimulation and TST.

Results: For ALS patients presenting with UMN in tested limb, the TST amplitude ratio was abnormal in 25 of 28 patients (89. Read More

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December 2018

Safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy.

Neural Regen Res 2019 Feb;14(2):313-318

Department of Neurology and Neurosurgery, School of Medicine, Collegium Medicum - University of Warmia and Mazury in Olsztyn; University Clinical Hospital in Olsztyn, Olsztyn, Poland.

Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have been shown to exhibit prospects in the treatment of amyotrophic lateral sclerosis. However, the safety of their clinical application needs to be validated. Read More

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February 2019

Oxidative stress: the lowest common denominator of multiple diseases.

Neural Regen Res 2019 Feb;14(2):238-241

Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Read More

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February 2019
0.234 Impact Factor

Amyotrophic lateral sclerosis: a complex syndrome that needs an integrated research approach.

Neural Regen Res 2019 Feb;14(2):193-196

CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases, Ministry of Economy and Competitiveness, Institute Carlos III), Madrid; Neurosciences Area, Institute Biodonostia; Department of Neurology, University Hospital Donostia, San Sebastián, Spain; Department of Neurosciences, University of the Basque Country, Universidad País Vasco-Euskal Herria Unibertsitatea, San Sebastián, Spain.

Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. Read More

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February 2019

Amyotrophic lateral sclerosis as a synaptopathy.

Neural Regen Res 2019 Feb;14(2):189-192

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA; School of Biomedical Sciences, The University of Queensland, St. Lucia, Australia.

The synapse is an incredibly specialized structure that allows for the coordinated communication of information from one neuron to another. When assembled into circuits, steady streams of excitatory and inhibitory synaptic activity shape neural outputs. At the organismal level, ensembles of neural networks underlie behavior, emotion and memory. Read More

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February 2019

Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula.

Neurology 2018 Dec 7. Epub 2018 Dec 7.

From the Departments of Functional Brain Imaging Research (H. Shinotoh, H. Shimada, K.T., S.K., M.O., Y. Kimura, S.H., M.I., N.S., T.S., M.H.) and Radiopharmaceuticals Development (M.-R.Z.), National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba; Neurology Clinic Chiba (H. Shinotoh); Kii ALS/PDC Research Center (Y. Kokubo), Mie University; Department of Neurology and Gerontology (F.N.), Graduate School of Medical Science, Kyoto Prefectural University of Medicine; Department of Psychiatry (S.K.), Nara Medical University; Division of Neurology (H.E.), Kobe University Graduate School of Medicine, Hyogo; Center for Development of Advanced Medicine for Dementia, Department of Neurology (Y. Kimura), National Institute for Geriatrics and Gerontology, Aichi; Department of Neurology (S.H.), Chiba University; and Department of Neuropathology (M.M.), Institute for Medical Science of Aging, Aichi Medical University, Japan.

Objective: To characterize the distribution of tau pathology in patients with amyotrophic lateral sclerosis/parkinsonism dementia complex on the Kii Peninsula (Kii ALS/PDC) by tau PET using [C]PBB3 as ligand.

Methods: This is a cross-sectional study of 5 patients with ALS/PDC and one asymptomatic participant with a dense family history of ALS/PDC from the Kii Peninsula who took part in this study. All were men, and their age was 76 ± 8 (mean ± SD) years. Read More

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December 2018

Pregnancy 5 Years After Onset of Amyotrophic Lateral Sclerosis Symptoms: A Case Report and Review of the Literature.

J Obstet Gynaecol Can 2018 Dec 7. Epub 2018 Dec 7.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON.

Background: Pregnancy in patients with amyotrophic lateral sclerosis (ALS) is extremely rare and often results in delivery of a healthy baby when patients are in the early stages of the disease.

Case: This report describes the case of a successful pregnancy 5 years after ALS onset. Significant worsening of weakness, unsteady balance, and dysphagia were noticed around the third trimester. Read More

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December 2018

Motor Unit Number Index (MUNIX) of hand muscles is a disease biomarker for adult spinal muscular atrophy.

Clin Neurophysiol 2018 Nov 24. Epub 2018 Nov 24.

Department of Neurology, Technische Universität Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany. Electronic address:

Objective: There is still insufficient knowledge about natural history in adult spinal muscular atrophy, thus valid markers for treatment and disease monitoring are urgently needed.

Methods: We studied hand muscle innervation pattern of 38 adult genetically confirmed 5q spinal muscular atrophy (SMA) patients by the motor unit number index (MUNIX) method. Data were compared to healthy controls and amyotrophic lateral sclerosis (ALS) patients and systematically correlated to typical disease-relevant scores and other clinical as well as demographic characteristics. Read More

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November 2018

Abnormal topological organization of structural covariance networks in amyotrophic lateral sclerosis.

Neuroimage Clin 2018 Nov 30. Epub 2018 Nov 30.

Department of Radiology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing 400030, PR China; Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing 400044, PR China. Electronic address:

Neuroimaging studies of patients with amyotrophic lateral sclerosis (ALS) have shown widespread alterations in structure, function, and connectivity in both motor and non-motor brain regions, suggesting multi-systemic neurobiological abnormalities that might impact large-scale brain networks. Here, we examined the alterations in the topological organization of structural covariance networks of ALS patients (N = 60) compared with normal controls (N = 60). We found that structural covariance networks of ALS patients showed a consistent rearrangement towards a regularized architecture evidenced by increased path length, clustering coefficient, small-world index, and modularity, as well as decreased global efficiency, suggesting inefficient global integration and increased local segregation. Read More

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November 2018

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort.

Neurobiol Aging 2018 Nov 3. Epub 2018 Nov 3.

Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Read More

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November 2018

Tryptophan 32 mediates SOD1 toxicity in a in vivo motor neuron model of ALS and is a promising target for small molecule therapeutics.

Neurobiol Dis 2018 Dec 4. Epub 2018 Dec 4.

Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada; Department of Medical Genetics, University of Alberta, Edmonton T6G 2H7, Canada. Electronic address:

SOD1 misfolding, toxic gain of function, and spread are proposed as a pathological basis of amyotrophic lateral sclerosis (ALS), but the nature of SOD1 toxicity has been difficult to elucidate. Uniquely in SOD1 proteins from humans and other primates, and rarely in other species, a tryptophan residue at position 32 (W32) is predicted to be solvent exposed and to participate in SOD1 misfolding. We hypothesized that W32 is influential in SOD1 acquiring toxicity, as it is known to be important in template-directed misfolding. Read More

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December 2018

Muscle specific kinase (MuSK) activation preserves neuromuscular junctions in the diaphragm but is not sufficient to provide a functional benefit in the SOD1 mouse model of ALS.

Neurobiol Dis 2018 Dec 4. Epub 2018 Dec 4.

Departments of Neuroscience, Genentech, South San Francisco, CA, USA. Electronic address:

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons, is characterized by rapid decline of motor function and ultimately respiratory failure. As motor neuron death occurs late in the disease, therapeutics that prevent the initial disassembly of the neuromuscular junction may offer optimal functional benefit and delay disease progression. To test this hypothesis, we treated the SOD1 mouse model of ALS with an agonist antibody to muscle specific kinase (MuSK), a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. Read More

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December 2018

A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats.

Cell Chem Biol 2018 Nov 5. Epub 2018 Nov 5.

Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 21 Stockholm, Sweden; Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain. Electronic address:

The expansion of GGGGCC repeats within the first intron of C9ORF72 constitutes the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Through repeat-associated non-ATG translation, these expansions are translated into dipeptide repeats (DPRs), some of which accumulate at nucleoli and lead to cell death. We here performed a chemical screen to identify compounds reducing the toxicity of ALS-related poly(PR) peptides. Read More

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November 2018

TDP-43 accelerates deadenylation of target mRNAs by recruiting Caf1 deadenylase.

FEBS Lett 2018 Dec 6. Epub 2018 Dec 6.

Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein, whose loss-of-function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Recent studies demonstrated that TDP-43 binds to the 3' UTR of target mRNAs to promote mRNA instability. Here, we show that TDP-43 recruits Caf1 deadenylase to mRNA targets and accelerates their deadenylation. Read More

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December 2018

The folding and aggregation energy landscapes of tethered RRM domains of human TDP-43 are coupled via a metastable molten globule-like oligomer.

Biochemistry 2018 Dec 6. Epub 2018 Dec 6.

Stress-induced misfolding and intraneuronal aggregation of the highly conserved nucleic acid binding protein TDP-43 (transactive response DNA binding protein 43 kDa) and its fragments have been implicated in amyotrophic lateral sclerosis and multiple other neurodegenerative diseases. However, the physico-chemical mechanism of its misfolding from the functional folded state is poorly understood. TDP-43 is a four domain protein and it performs the essential nucleic acid binding function with the help of its two tandem RNA recognition motif domains naturally tethered by a linker (called here tethered RRM domain of TDP-43 or TDP-43). Read More

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December 2018

Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: A systematic review and meta-analysis.

J Neurochem 2018 Dec 6. Epub 2018 Dec 6.

Department of Neurology, Gold Coast Hospital and Health Service, QLD, Australia.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that results from motor neuron damage. Cannabinoids have been proposed as treatments for ALS due to their anti-excitotoxicity, anti-oxidant, and anti-inflammatory effects. Pre-clinical studies in mice models of ALS have been published using a range of cannabinoid formulations and doses. Read More

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December 2018

ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death.

Front Immunol 2018 14;9:2647. Epub 2018 Nov 14.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Shanghai, China.

Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human (Optineurin), particularly E478G, have been found in many ALS patients. Read More

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November 2018
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A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis.

Sci Transl Med 2018 Dec;10(470)

Neurimmune AG, 8952 Schlieren, Switzerland.

Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 and cause familial amyotrophic lateral sclerosis (FALS). However, the implications of wild-type SOD1 misfolding in sporadic forms of ALS (SALS) remain unclear. By screening human memory B cells from a large cohort of healthy elderly subjects, we generated a recombinant human monoclonal antibody (α-miSOD1) that selectively bound to misfolded SOD1, but not to physiological SOD1 dimers. Read More

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December 2018
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Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA).

Brain Sci 2018 Dec 4;8(12). Epub 2018 Dec 4.

School of Medicine, Keele University, Staffordshire ST5 5BG, UK.

Unravelling the complex molecular pathways responsible for motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) remains a persistent challenge. Interest is growing in the potential molecular similarities between these two diseases, with the hope of better understanding disease pathology for the guidance of therapeutic development. The aim of this study was to conduct a comparative analysis of published proteomic studies of ALS and SMA, seeking commonly dysregulated molecules to be prioritized as future therapeutic targets. Read More

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December 2018
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TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides.

Bioorg Chem 2018 Nov 27;84:254-259. Epub 2018 Nov 27.

Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China; Beijing Institute for Brain Disorders, Beijing 100069, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China. Electronic address:

TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. Read More

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November 2018
2 Reads

Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.

Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process.

Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline.

Design, Setting, And Participants: In this case-control study, we investigated NFL levels in CSF obtained from controls and patients with several neurodegenerative diseases. Read More

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December 2018

Clinical and Genetic Features of Patients with Juvenile Amyotrophic Lateral Sclerosis with Fused in Sarcoma (FUS) Mutation.

Med Sci Monit 2018 Dec 3;24:8750-8757. Epub 2018 Dec 3.

Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).

BACKGROUND Juvenile amyotrophic lateral sclerosis (JALS) is a rare form of motor neuron disease and occurs before 25 years of age. Only a few cases of juvenile-onset ALS have been reported. MATERIAL AND METHODS To study genetic and clinicopathological features in Chinese patients with juvenile ALS, we retrospectively reviewed ALS patients in our hospital and screened out 2 patients with disease onset before the age of 25. Read More

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December 2018

Advances in acoustic monitoring and control of focused ultrasound-mediated increases in blood-brain barrier permeability.

Br J Radiol 2018 Dec 3:20180601. Epub 2018 Dec 3.

1 Physical Sciences Platform, Sunnybrook Research Institute , Toronto, ON , Canada.

Transcranial focused ultrasound (FUS) combined with intravenously circulating microbubbles can transiently and selectively increase blood-brain barrier permeability to enable targeted drug delivery to the central nervous system, and is a technique that has the potential to revolutionize the way neurological diseases are managed in medical practice. Clinical testing of this approach is currently underway in patients with brain tumors, early Alzheimer's disease, and amyotrophic lateral sclerosis. A major challenge that needs to be addressed in order for widespread clinical adoption of FUS-mediated blood-brain barrier permeabilization to occur is the development of systems and methods for real-time treatment monitoring and control, to ensure that safe and effective acoustic exposure levels are maintained throughout the procedures. Read More

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December 2018
2 Reads

Edaravone acts as a potential therapeutic drug against pentylenetetrazole-induced epilepsy in male albino rats by downregulating cyclooxygenase-II.

Brain Behav 2018 Dec 1:e01156. Epub 2018 Dec 1.

Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.

Introduction: The effects of edaravone against pentylenetetrazole (PTZ)-induced epilepsy in male albino rats were investigated. Edaravone is a well-known commercial drug used in the treatment of strokes and amyotrophic lateral sclerosis (ALS). Antioxidant and free radical scavenging activities of edaravone have been reported in patients with ALS. Read More

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December 2018

The applause sign in frontotemporal lobar degeneration and related conditions.

J Neurol 2018 Dec 1. Epub 2018 Dec 1.

Neurologische Klinik und Poliklinik, Ludwig Maximilians Universität München, Munich, Germany.

The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Read More

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December 2018

Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway.

Neurotoxicology 2018 Nov 29;71:6-15. Epub 2018 Nov 29.

Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, "Federico II" University of Naples, Naples 80131, Italy; Division of Pharmacology, Department of Science and Technology, University of Sannio, 82100 Benevento, Italy. Electronic address:

In humans, mutation of glycine 93 to alanine of Cu/Zn superoxide dismutase type-1 (SOD1-G93 A) has been associated to some familial cases of Amyotrophic Lateral Sclerosis (ALS). Several evidence proposed the involvement of environmental pollutants that like mercury could accelerate ALS symptoms. SH-SY5Y cells stably transfected with SOD1 and G93 A mutant of SOD1 constructs were exposed to non-toxic concentrations (0. Read More

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November 2018

Satisfaction of patients with amyotrophic lateral sclerosis with an oral appliance for managing oral self-biting injuries and alterations in their masticatory system: A case-series study.

J Prosthet Dent 2018 Nov 30. Epub 2018 Nov 30.

Full Professor, Department of Prosthodontics, School of Dentistry, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; and Researcher, Oral Health and Masticatory System Group (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Statement Of Problem: About 10% of patients with amyotrophic lateral sclerosis (ALS) are candidates for oral treatment specifically because of traumatic injuries in the lips, cheeks, or tongue due to self-biting. However, patients with ALS have a prevalence of temporomandibular disorder (TMD) similar to that in the general population.

Purpose: The purpose of this case-series study was to determine the degree of satisfaction of patients with ALS with an oral appliance for managing oral self-biting lesions or symptoms related to TMDs. Read More

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November 2018

Amyotrophy of the first dorsal interosseous muscle or sign of the double anatomical snuffbox, diagnostic clue in amyotrophic lateral sclerosis.

Med Clin (Barc) 2018 Nov 27. Epub 2018 Nov 27.

Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España. Electronic address:

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November 2018

Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System.

Neuroimmunomodulation 2018 Dec 5:1-25. Epub 2018 Dec 5.

Neuroscience Program, Federal Fluminense University, Niterói, Brazil.

An extensive microglial-astrocyte-monocyte-neuronal cross talk seems to be crucial for normal brain function, development, and recovery. However, under certain conditions neuroinflammatory interactions between brain cells and neuroimmune cells influence disease outcome and brain pathology. Microglial cells express a range of functional states with dynamically pleomorphic profiles from a surveilling status of synaptic transmission to an active player in major events of development such as synaptic elimination, regeneration, and repair. Read More

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December 2018
4 Reads

Impaired Verbal Communication: diagnosis review in patients with Amyotrophic Lateral Sclerosis.

Rev Bras Enferm 2018 Nov-Dec;71(6):3063-3073

Universidade Federal do Ceará. Fortaleza, Ceará, Brazil.

Objective: To review the contents of the nursing diagnosis of Impaired Verbal Communication in patients with Amyotrophic Lateral Sclerosis.

Method: For the review of this diagnosis we used the integrative review. The 21 selected articles were submitted to a careful concept analysis for the definition of the diagnostic concept and review of its elements. Read More

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October 2017
1 Read

Dynamin-related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases.

J Cell Physiol 2018 Dec 4. Epub 2018 Dec 4.

Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China.

Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin-related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1-dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid β (Aβ) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1-associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Drp1 is required for mitochondrial division determining the size, shape, distribution, and remodeling as well as maintaining of mitochondrial integrity in mammalian cells. Read More

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December 2018

Fungal Neurotoxins and Sporadic Amyotrophic Lateral Sclerosis.

Neurotox Res 2018 Dec 5. Epub 2018 Dec 5.

Neuroinflammation Group, Department of Biological Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis (ALS). ALS is the most common form of motor neuron disease (MND) in adults. It is a progressive and fatal disease. Read More

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December 2018

Taste changes in amyotrophic lateral sclerosis and effects on quality of life.

Neurol Sci 2018 Dec 4. Epub 2018 Dec 4.

Neuromuscular Omnicentre (NEMO)-Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy.

The primary aim of the study is to evaluate possible taste changes in a cohort of amyotrophic lateral sclerosis patients (pALS) with dysphagia, focusing on eventual psychological and quality of life (QoL) implications. The second aim is to evaluate the changes of QoL following the use of a specific device that provides food flavour. Thirty-two ALS patients were recruited and divided into two groups: subjects feeding only through enteral tube (ET) and subjects still eating by oral way (OW). Read More

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December 2018
2 Reads

Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing.

Sci Signal 2018 Dec 4;11(559). Epub 2018 Dec 4.

Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.

The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in , which encodes p62, are linked to hereditary inflammatory conditions such as Paget's disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62 We found that p62, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapamycin complex 1 (mTORC1). Read More

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December 2018

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders.

Int J Mol Sci 2018 Nov 30;19(12). Epub 2018 Nov 30.

Institute of Biomedical and Clinical Sciences (IBCS), College of Medicine and Health (CMH), St. Luke's Campus, University of Exeter, Exeter EX4 4QL, UK.

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91 and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation-primarily superoxide anion (O₂), although hydrogen peroxide (H₂O₂) can also be generated. Read More

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November 2018
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The Hairpin Form of r(GC) in c9ALS/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules.

Cell Chem Biol 2018 Nov 29. Epub 2018 Nov 29.

Departments of Chemistry and Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address:

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded GC repeat [(GC)] in C9ORF72. ALS/FTD-associated toxicity has been traced to the RNA transcribed from the repeat expansion [r(GC)], which sequesters RNA-binding proteins (RBPs) and undergoes repeat-associated non-ATG (RAN) translation to generate toxic dipeptide repeats. Using in vitro and cell-based assays, we identified a small molecule (4) that selectively bound r(GC), prevented sequestration of an RBP, and inhibited RAN translation. Read More

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November 2018

50-Hz Magnetic Field Impairs the Expression of Iron-related Genes in the in vitro SOD1 Model of Amyotrophic Lateral Sclerosis.

Int J Radiat Biol 2018 Dec 4:1-28. Epub 2018 Dec 4.

a Division of Health Protection Technologies , ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development , 00123 Rome , Italy ;

Purpose: we characterized the response to the extremely low frequency magnetic field (ELF-MF) in an in vitro model of familial Amyotrophic Lateral Sclerosis (fALS), carrying two mutant variants of the superoxide dismutase 1 (SOD1) gene.

Materials And Methods: SH-SY5Y human neuroblastoma cells, stably over-expressing the wild type, the G93A or the H46R mutant SOD1 cDNA, were exposed to either the ELF-MF (50 Hz, 1 mT) or the sham control field, up to 72 hours. Analysis of i) viability, proliferation and apoptosis, ii) reactive oxygen species generation, and iii) assessment of the iron metabolism, were carried out in all clones in response to the MF exposure. Read More

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December 2018
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Moral judgment in patients with behavioral variant of frontotemporal dementia and amyotrophic lateral sclerosis: no impairment of the moral position, but rather its execution.

Amyotroph Lateral Scler Frontotemporal Degener 2018 Dec 4:1-7. Epub 2018 Dec 4.

a Department of Neurology , University of Ulm , Ulm , Germany and.

Objective: To investigate moral judgment competence in patients with the behavioral variant frontotemporal dementia (bvFTD) compared to amyotrophic lateral sclerosis (ALS) and controls.

Methods: N = 12 bvFTD, N = 22 ALS patients and N = 19 neurological unimpaired controls were examined. In the 'Moral Competence Test' (MCT), participants had to evaluate two moral dilemmas by predefined arguments to measure the consistency of their moral judgments. Read More

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December 2018
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Amyotrophic lateral sclerosis of long clinical course clinically presenting with progressive muscular atrophy.

Neuropathology 2018 Dec 3. Epub 2018 Dec 3.

Department of Neurology, Mifukai Vihara Hananosato Hospital, Hiroshima, Japan.

Amyotrophic lateral sclerosis (ALS) primarily affects upper and lower motor neurons. Phosphorylated trans-activation response DNA-binding protein of 43 kDa (TDP-43) inclusion bodies are reportedly a pathological hallmark of sporadic ALS. Here, we present an atypical case of sporadic ALS that progressed very slowly, persisted for 19 years, and clinically appeared to only affect the lower motor neurons; however, upper motor neuron degeneration was detected at autopsy. Read More

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December 2018

Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology.

Acta Neuropathol 2018 Dec 3. Epub 2018 Dec 3.

Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Read More

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December 2018
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The multidimensional nature of dyspnoea in amyotrophic lateral sclerosis patients with chronic respiratory failure: Air hunger, anxiety and fear.

Respir Med 2018 Dec 17;145:1-7. Epub 2018 Oct 17.

Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du Département R3S, F-75013, Paris, France.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to chronic respiratory failure. Few studies have investigated ALS-related dyspnoea, and none have characterised the emotional distress it inflicts. We hypothesised that ALS-related dyspnoea has a strong affective component that relates to quality of life. Read More

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December 2018

Disease-modifying effects of metabolic perturbations in ALS/FTLD.

Mol Neurodegener 2018 Dec 4;13(1):63. Epub 2018 Dec 4.

Department of Neurology, The McGovern Medical School of UT Health, Houston, TX, USA.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are characterized by the accumulation of pathological protein aggregates that contain a number of proteins, most notably TAR DNA binding protein 43 kDa (TDP-43). Surprisingly, recent clinical studies suggest that dyslipidemia, high body mass index, and type 2 diabetes mellitus are associated with better clinical outcomes in ALS. Read More

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December 2018
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[The case of the fulminant course of amyotrophic lateral sclerosis].

Zh Nevrol Psikhiatr Im S S Korsakova 2018 ;118(10):63-65

Federal State Budgetary Scientific Institution 'East-Siberian Institute of Medical and Ecological Research', Angarsk, Russia.

The authors report the case of a lightning-fast course of amyotrophic lateral sclerosis (ALS) in a 49-year female patient. The diagnosis was based on complaints, clinical picture, electroneuromyography and tomography of the cervical spine. The nature of the course of the disease was fulminant, since 6 months passed from the onset of the first symptoms to the pronounced process, and then to the fatal outcome. Read More

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January 2018
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Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome.

J Neurol 2018 Nov 29. Epub 2018 Nov 29.

French Reference Center of Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France.

Objective: To present clinical, radiological, and pathological features of a cohort of patients with motor neuron involvement in association with anti-Ma2 antibodies (Ma2-Ab).

Methods: Retrospective case-series of patients with definite paraneoplastic neurological syndrome (PNS) and Ma2-Ab, and cases identified from a review of the literature.

Results: Among 33 Ma2-Ab patients referred between 2002 and 2016, we retrospectively identified three patients (9. Read More

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November 2018