Elevated methylation levels, reduced expression levels, and frequent contractions in a clinical cohort of C9orf72 expansion carriers

A repeat expansion in the C9orf72-SMCR8 complex subunit (C9orf72) is the most common genetic cause of two debilitating neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (...
Source: Molecular Neurodegeneration - Category: Neurology Authors: Tags: Research article Source Type: research

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Publication date: Available online 29 February 2020Source: Journal of Molecular BiologyAuthor(s): Rebecca L. Casterton, Rachel J. Hunt, Manolis Fanto
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research
Primary lateral sclerosis (PLS) is a rare type of motor neuron disease (MND) characterized by the loss of upper motor neurons without lower motor neuron involvement [1]. In contrast, amyotrophic lateral sclerosis (ALS) is a common type of MND that is occasionally complicated by frontotemporal dementia (FTD) as the TDP-43 proteinopathy. However, there are few studies on the relationship of PLS with ALS, FTD and TDP-43 proteinopathy because of the rarity of autopsy cases. Here, we report a 68-year-old woman who exhibited typical clinical symptoms of PLS at onset, which then progressed to FTD, although her pathological diagno...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Abstract The deposition of proteins of abnormal conformation is one of the major hallmarks of the common neurodegenerative diseases including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, frontotemporal dementia, and prion diseases. Protein quality control systems have evolved to protect cells and organisms against the harmful consequences of abnormally folded proteins that are constantly produced in small amounts. Mutations in rare inherited forms of neurodegenerative diseases have provided compelling evidence that failure of protein quality control systems can drive neurodegeneration. With extensive k...
Source: Current Opinion in Neurobiology - Category: Neurology Authors: Tags: Curr Opin Neurobiol Source Type: research
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal late-onset neurodegenerative disease that specifically affects the function and survival of spinal and cortical motor neurons. ALS shares many genetic, clinical, and pathological characteristics with frontotemporal dementia (FTD), and these diseases are now recognized as presentations of a disease spectrum known as ALS/FTD. The molecular determinants of neuronal loss in ALS/FTD are still debated, but the recent discovery of nucleocytoplasmic transport defects as a common denominator of most if not all forms of ALS/FTD has dramatically changed our understandin...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Abstract Exploring the neurochemical continuum between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with respect to monoamines and kynurenines in cerebrospinal fluid (CSF) and serum, may be useful to identify possible new research/therapeutic targets. Hence, we analysed monoamines and kynurenines in CSF and serum derived from patients with FTD (n = 39), ALS (n = 23), FTD-ALS (n = 4) and age-matched control subjects (n = 26), using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) with electrochemical detection (EC...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Conditions:   Motor Neuron Disease, Familial;   Amyotrophic Lateral Sclerosis With Dementia Interventions:   Device: Anodal bilateral motor cortex and cathodal spinal tDCS;   Device: Sham bilateral motor cortex and sham spinal tDCS Sponsor:   Azienda Ospedaliera Spedali Civili di Brescia Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 29 February 2020Source: Journal of Molecular BiologyAuthor(s): Rebecca L. Casterton, Rachel J. Hunt, Manolis Fanto
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research
We describe how tau becomes hyperphosphorylated and oligomerized as part of an endogenous mechanism to promote the translational stress response through interaction with RNA binding proteins. Prior studies demonstrate that dysfunction of RNA binding proteins biology is sufficient to cause neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Emerging evidence indicates that tau-mediated neurodegeneration also occurs through a mechanism that is mediated by RNA binding proteins and the translational stress response. Discovery of the role of RNA metabolism in tauopathy opens a wide var...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. Th...
Source: Molecular Neurodegeneration - Category: Neurology Authors: Tags: Research article Source Type: research
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