4,175 results match your criteria Dementia in Motor Neuron Disease


Association Between Globular Glial Tauopathies and Frontotemporal Dementia-Expanding the Spectrum of Gliocentric Disorders: A Review.

JAMA Neurol 2021 Jun 21. Epub 2021 Jun 21.

Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.

Importance: Globular glial tauopathies (GGTs), as defined by a consensus study in 2013, belong to the group of frontotemporal lobar degenerations and expand the spectrum of glial-predominant neurodegenerative diseases. Three neuropathological subtypes of GGT (types I-III) are characterized by phosphorylated tau-immunopositive inclusions that are predominantly in oligodendroglia and/or astroglia in the frontal, temporal, and/or precentral cortices. Type II is largely restricted to the corticospinal system. Read More

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Climate change and neurodegenerative diseases.

Environ Res 2021 Jun 12;201:111511. Epub 2021 Jun 12.

Scuola Superiore Sant'Anna and Centre for Climate Change Studies and Sustainable Actions (3CSA), Pisa, Italy.

The climate change induced global warming, and in particular the increased frequency and intensity of heat waves, have been linked to health problems. Among them, scientific works have been reporting an increased incidence of neurological diseases, encompassing also neurodegenerative ones, such as Dementia of Alzheimer's type, Parkinson's Disease, and Motor Neuron Diseases. Although the increase in prevalence of neurodegenerative diseases is well documented by literature reports, the link between global warming and the enhanced prevalence of such diseases remains elusive. Read More

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Dissection, in vivo imaging and analysis of the mouse epitrochleoanconeus muscle.

J Anat 2021 Jun 13. Epub 2021 Jun 13.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.

Analysis of rodent muscles affords an opportunity to glean key insights into neuromuscular development and the detrimental impact of disease-causing genetic mutations. Muscles of the distal leg, for instance the gastrocnemius and tibialis anterior, are commonly used in such studies with mice and rats. However, thin and flat muscles, which can be dissected, processed and imaged without major disruption to muscle fibres and nerve-muscle contacts, are more suitable for accurate and detailed analyses of the peripheral motor nervous system. Read More

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NMJ-Analyser identifies subtle early changes in mouse models of neuromuscular disease.

Sci Rep 2021 Jun 10;11(1):12251. Epub 2021 Jun 10.

MRC Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, University College London, London, WC1E 6BT, UK.

The neuromuscular junction (NMJ) is the peripheral synapse formed between a motor neuron axon terminal and a muscle fibre. NMJs are thought to be the primary site of peripheral pathology in many neuromuscular diseases, but innervation/denervation status is often assessed qualitatively with poor systematic criteria across studies, and separately from 3D morphological structure. Here, we describe the development of 'NMJ-Analyser', to comprehensively screen the morphology of NMJs and their corresponding innervation status automatically. Read More

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Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis.

Nat Commun 2021 06 7;12(1):3396. Epub 2021 Jun 7.

German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.

Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with overlapping clinical features and the pathological hallmark of cytoplasmic deposits of misfolded proteins. The most frequent cause of familial forms of these diseases is a hexanucleotide repeat expansion in the non-coding region of the C9ORF72 gene that is translated into dipeptide repeat polymers. Here we show that proline/arginine repeat polymers derail protein folding by sequestering molecular chaperones. Read More

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Novel Optineurin Frameshift Insertion in a Family With Frontotemporal Dementia and Parkinsonism Without Amyotrophic Lateral Sclerosis.

Front Neurol 2021 19;12:645913. Epub 2021 May 19.

Department of Neurology, National Neuroscience Institute, Singapore, Singapore.

Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (), granulin precursor (), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin () have rarely been reported. Read More

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Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.

Adv Sci (Weinh) 2021 Jun 3:e2101090. Epub 2021 Jun 3.

School of Pharmacy, Henan University, Kaifeng, 475001, China.

The blood-brain barrier (BBB) is a highly specialized neurovascular unit, initially described as an intact barrier to prevent toxins, pathogens, and potentially harmful substances from entering the brain. An intact BBB is also critical for the maintenance of normal neuronal function. In cerebral vascular diseases and neurological disorders, the BBB can be disrupted, contributing to disease progression. Read More

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Physical Exercise-Induced Myokines in Neurodegenerative Diseases.

Int J Mol Sci 2021 May 28;22(11). Epub 2021 May 28.

Department of Biological Sciences, Konkuk University, Seoul 05029, Korea.

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Read More

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Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases.

Int J Mol Sci 2021 May 18;22(10). Epub 2021 May 18.

Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.

The number of patients with neurodegenerative diseases (NDs) is increasing, along with the growing number of older adults. This escalation threatens to create a medical and social crisis. NDs include a large spectrum of heterogeneous and multifactorial pathologies, such as amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple system atrophy, and the formation of inclusion bodies resulting from protein misfolding and aggregation is a hallmark of these disorders. Read More

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Characterization of a Mouse Model of Alzheimer's Disease Expressing Aβ4-42 and Human Mutant Tau.

Int J Mol Sci 2021 May 14;22(10). Epub 2021 May 14.

Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D-37075 Göttingen, Germany.

The relationship between the two most prominent neuropathological hallmarks of Alzheimer's Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Read More

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Highlighting the protective or degenerative role of AMPK activators in dementia experimental models.

CNS Neurol Disord Drug Targets 2021 May 26. Epub 2021 May 26.

Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a driving or deterrent factor in the development of neurodegenerative diseases and dementia. AMPK affects intracellular proteins like the mammalian target of rapamycin (mTOR). Peroxisome proliferator-activated receptor-γ coactivator 1-α (among others) contributes to a wide range of intracellular activities based on its downstream molecules such as energy balancing (ATP synthesis), extracellular inflammation, cell growth, and neuronal cell death (such as apoptosis, necrosis, and necroptosis). Read More

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Prevalence of multimorbidity and its impact on survival in people with motor neuron disease.

Eur J Neurol 2021 May 25. Epub 2021 May 25.

Anne Rowling Regenerative Neurology Clinic, Chancellor's Building, University of Edinburgh, Edinburgh, UK.

Background And Purpose: This study was undertaken to determine the prevalence of multimorbidity in people with motor neuron disease (MND) and to identify whether specific patterns of multimorbidity impact survival beyond age alone.

Methods: We performed a retrospective analysis of the Scottish national MND register from 1 January 2015 to 29 October 2019. People with amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy were included. Read More

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The clinical spectrum of multisystem proteinopathy: Data from a neurodegenerative cohort.

J Neurol Sci 2021 07 4;426:117478. Epub 2021 May 4.

Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40123 Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, 40139 Bologna, Italy. Electronic address:

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What Is the Role of the Cytosolic DNA Response in Neurodegeneration?

Neurology 2021 05;96(20):940-943

From the Mayo Clinic, Rochester, MN.

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Genetic testing in motor neuron disease and frontotemporal dementia: a 5-year multicentre evaluation.

J Med Genet 2021 May 7. Epub 2021 May 7.

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

Introduction: Motor neuron disease (MND) and frontotemporal dementia (FTD) comprise a neurodegenerative disease spectrum. Genetic testing and counselling is complex in MND/FTD owing to incomplete penetrance, variable phenotype and variants of uncertain significance. Affected patients and unaffected relatives are commonly referred to clinical genetics to consider genetic testing. Read More

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Generation of Cortical, Dopaminergic, Motor, and Sensory Neurons from Human Pluripotent Stem Cells.

Methods Mol Biol 2021 May 7. Epub 2021 May 7.

Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore, Singapore.

The use of patient-derived induced pluripotent stem cells (iPSCs) and their neural derivatives is becoming increasingly important in the study of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, peripheral neuropathy, and so on. Increasingly, iPSC-derived neurons also reveal key pathways and signaling defects in psychiatric disorders such as autism spectrum disorders, schizophrenia, and bipolar disorder. With recent advances in CRISPR/Cas9-mediated genome editing technology, patient-derived iPSCs with disease-causing mutations can be corrected into "isogenic control lines," and these can be differentiated into neural derivatives with identical genetic background. Read More

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Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Health Research Building, Discovery Way, Murdoch 6150, Australia.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. Read More

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Progressive apraxia of speech: delays to diagnosis and rates of alternative diagnoses.

J Neurol 2021 May 4. Epub 2021 May 4.

Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.

Background: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder of speech programming distinct from aphasia and dysarthria, most commonly associated with a 4-repeat tauopathy. Our objective was to better understand the reasons for possible delays or diagnostic errors for patients with PAOS.

Methods: Seventy-seven consecutive PAOS research participants from the Neurodegenerative Research Group were included in this study. Read More

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Lymphoblastoid Cell Lines as Models to Study Mitochondrial Function in Neurological Disorders.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC 3086, Australia.

Neurological disorders, including neurodegenerative diseases, are collectively a major cause of death and disability worldwide. Whilst the underlying disease mechanisms remain elusive, altered mitochondrial function has been clearly implicated and is a key area of study in these disorders. Studying mitochondrial function in these disorders is difficult due to the inaccessibility of brain tissue, which is the key tissue affected in these diseases. Read More

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Supramolecular Polymorphism of (GC) Repeats Associated with ALS and FTD.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Department of Complex Matter, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.

Guanine-rich DNA sequences self-assemble into highly stable fourfold structures known as DNA-quadruplexes (or G-quadruplexes). G-quadruplexes have furthermore the tendency to associate into one-dimensional supramolecular aggregates termed G-wires. We studied the formation of G-wires in solutions of the sequences d(GC) with = 1, 2, and 4. Read More

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Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3QX, UK.

Neurodegenerative diseases (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. Read More

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Histone Methylation Regulation in Neurodegenerative Disorders.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.

Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation and histone posttranslational modifications, which are critical for gene expression in almost all tissues and in brain health and disease. These advances have influenced much interest in understanding the dysregulation of epigenetic mechanisms in neurodegenerative disorders. Although these disorders diverge in their fundamental causes and pathophysiology, several involve the dysregulation of histone methylation-mediated gene expression. Read More

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Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis-A Retrospective Cohort Study.

J Clin Med 2021 Apr 12;10(8). Epub 2021 Apr 12.

Department of Neurology with Institute of Translational Neurology, Münster University Hospital (UKM), 48149 Münster, Germany.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS.

Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Read More

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Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.

Proteasomal dysfunction is known to be associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). Our previous reports have shown that a mutant form of ubiquilin-2 (UBQLN2) linked to ALS/FTD leads to neurodegeneration accompanied by accumulations of the proteasome subunit Rpt1 in transgenic rats, but the precise pathogenic mechanisms of how this mutation impairs the proteasome remains to be elucidated. Here, we reveal that this UBQLN2 mutation in rats disrupted the proteasome integrity prior to neurodegeneration, that it dissociated the 26S proteasome in vitro, and that its depletion did not affect 26S proteasome assembly. Read More

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Pathway from TDP-43-Related Pathology to Neuronal Dysfunction in Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

Department of Neurology, Nagoya University, Nagoya 744-8550, Japan.

Transactivation response DNA binding protein 43 kDa (TDP-43) is known to be a pathologic protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43 is normally a nuclear protein, but affected neurons of ALS or FTLD patients exhibit mislocalization of nuclear TDP-43 and cytoplasmic inclusions. Basic studies have suggested gain-of-neurotoxicity of aggregated TDP-43 or loss-of-function of intrinsic, nuclear TDP-43. Read More

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The Prevalence and Management of Saliva Problems in Motor Neuron Disease: A 4-Year Analysis of the Scottish Motor Neuron Disease Register.

Neurodegener Dis 2020 26;20(4):147-152. Epub 2021 Apr 26.

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Introduction: Saliva problems are common and distressing for people with motor neuron disease (pwMND). Despite clinical guidelines for assessment and treatment, management of saliva problems has received little research attention.

Objective: We aimed to investigate the prevalence of saliva problems in pwMND, their association with clinical factors, and their management practice using a highly curated population-based register for motor neuron disease (MND) with 99% case ascertainment. 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 05 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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Altered perivascular fibroblast activity precedes ALS disease onset.

Nat Med 2021 04 15;27(4):640-646. Epub 2021 Apr 15.

University of Ulm, Neurology Clinic, Ulm, Germany.

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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Connecting TDP-43 Pathology with Neuropathy.

Trends Neurosci 2021 Jun 5;44(6):424-440. Epub 2021 Apr 5.

Department of Stem Cell and Regenerative Biology, Department of Molecular and Cellular Biology, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Transactive response DNA-binding protein 43 kDa (TDP-43), a multifunctional nucleic acid-binding protein, is a primary component of insoluble aggregates associated with several devastating nervous system disorders; mutations in TARDBP, its encoding gene, are a cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we review established and emerging roles of TDP-43 and consider how its dysfunction impinges on RNA homeostasis in the nervous system, thereby contributing to neural degeneration. Notably, improper splicing of the axonal growth-associated factor STMN2 has recently been connected to TDP-43 dysfunction, providing a mechanistic link between TDP-43 proteinopathies and neuropathy. Read More

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