Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: a Link to Neurodegeneration

AbstractAmyotrophic lateral sclerosis (ALS) is a disease caused by the degeneration of motor neurons (MNs) leading to progressive muscle weakness and atrophy. Several molecular pathways have been implicated, such as glutamate-mediated excitotoxicity, defects in cytoskeletal dynamics and axonal transport, disruption of RNA metabolism, and impairments in proteostasis. ALS is associated with protein accumulation in the cytoplasm of cells undergoing neurodegeneration, which is a hallmark of the disease. In this review, we focus on mechanisms of proteostasis, particularly protein degradation, and discuss how they are related to the genetics of ALS. Indeed, the genetic bases of the disease with the implication of more than 30 genes associated with familial ALS to date, together with the important increase in understanding of endoplasmic reticulum (ER) stress, proteasomal degradation, and autophagy, allow researchers to better understand the mechanisms underlying the selective death of motor neurons in ALS. It is clear that defects in proteostasis are involved in this type of cellular degeneration, but whether or not these mechanisms are primary causes or merely consequential remains to be clearly demonstrated. Novel cellular and animal models allowing chronic expression of mutant proteins, for example, are required. Further studies linking genetic discoveries in ALS to mechanisms of protein clearance will certainly be crucial in order to accelerate translational and clinical resear...
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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AbstractInsoluble aggregates containing TDP-43 are widely observed in the diseased brain, and defined as “TDP-43 pathology” in a spectrum of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and ALS with frontotemporal dementia. Here we report that Betz cells of patients with TDP-43 pathology display a distinct set of intracellular defects especially at the site of nuclear membrane, mitochondria and endoplasmic reticulum (ER). Numerous TDP-43 mouse models have been generated to discern the cellular and molecular basis of the disease, but mechanisms of neuronal vu...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
ConclusionsThe prognosis of ALS-related ARF requiring ICU admission resembles that of ARF complicating other conditions with high short-term mortality (e.g. lung cancer).
Source: Journal of Critical Care - Category: Gastroenterology Source Type: research
OBJECTIVE: In Amyotrophic lateral sclerosis (ALS), disease severity, ineffective treatment, and increasing dependence on caregivers may give rise to hopelessness and suicidal ideation among patients. In clinical practice, the desire for death among patient...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
Publication date: Available online 16 November 2018Source: Neuroscience ResearchAuthor(s): Takashi Hosaka, Takenari Yamashita, Sayaka Teramoto, Naoki Hirose, Akira Tamaoka, Shin KwakAbstractCurrently, no reliable biomarkers of amyotrophic lateral sclerosis (ALS) exist. In sporadic ALS, RNA editing at the glutamine/arginine site of GluA2 mRNA is specifically reduced in the motor neurons due to the downregulation of adenosine deaminase acting on RNA 2 (ADAR2). Furthermore, TDP-43 pathology, the pathological hallmark of ALS, is observed in the ADAR2-lacking motor neurons in ALS patients and conditional ADAR2 knockout mice, su...
Source: Neuroscience Research - Category: Neuroscience Source Type: research
AbstractClassification of neurodegenerative diseases (NDD) like Parkinson ’s disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s disease (HD) is of high clinical importance. The gait analysis based classification is attractive due to its simplicity and noninvasiveness. In this paper, we propose a data driven features approach along with autocorrelation and cross correlation between gait time series to create different feature set for a sample representation. Further, a rule based classifier using Decision Tree is trained with those features to classify the neurodegenerative diseases from healthy...
Source: Health and Technology - Category: Information Technology Source Type: research
Amyotrophic lateral sclerosis — a multisystem neurodegenerative disorderAmyotrophic lateral sclerosis — a multisystem neurodegenerative disorder, Published online: 16 November 2018; doi:10.1038/s41582-018-0103-yAmyotrophic lateral sclerosis (ALS) is a progressive motor disorder, and many patients also show non-motor symptoms including executive, behavioural and language dysfunction. A new study demonstrates a robust relationship between progression of these non-motor symptoms and declining motor disease in patients with ALS, providing important insights into mechanisms of ALS pathogenesis.
Source: Nature Reviews Neurology - Category: Neurology Authors: Source Type: research
elo G Abstract Apathy is recognized as the most common behavioral change in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disorder. Particularly, apathy has been reported to be associated with poor ALS prognosis. However, the brain microstructural correlates of this behavioral symptom, reported as the most common in ALS, have not been completely elucidated. Using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS), here we aimed to quantify the correlation between brain microstructural damage and apathy scores in the early st...
Source: Behavioural Neurology - Category: Neurology Authors: Tags: Behav Neurol Source Type: research
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that occurs in 4 among 100 000 people in the United States. Individuals with ALS gradually lose their ability to control voluntary muscles, diminishing their ability to communicate. A comprehensive multidatabase search retrieved 31 qualitative research articles that addressed persons with end-of-life experiences with ALS. Inclusion/exclusion criteria were applied and a critical appraisal was applied for the final 8 included articles. First-person data extraction from the final articles represented emergence of 3 themes significant to persons with ALS: deci...
Source: Holistic Nursing Practice - Category: Nursing Tags: FEATURES Source Type: research
Amyotrophic lateral sclerosis (ALS) represents a devastating, progressive, heterogeneous, and the most common motor neuron (MN) disease. To date, no cure has been available for the condition. Studies with tran...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
Abstract The protein level of muscle-specific human NogoA is abnormally upregulated in amyotrophic lateral sclerosis (ALS) mice and patients. On the other hand, while the presence of miR-206 in muscle cells delays onset and death in ALS, the relationship between these two phenomena remains unclear. Mammalian NogoA protein, also known as Reticulon 4a (Rtn4a), plays an important role in inhibiting the outgrowth of motor neurons. Our group previously identified zebrafish rtn4al as the target gene of miR-206 and found that knockdown of miR-206 increases rtn4al mRNA and Rtn4al protein in zebrafish embryos. It can be co...
Source: Marine Biotechnology - Category: Biotechnology Authors: Tags: Mar Biotechnol (NY) Source Type: research
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