Decoding ALS: from genes to mechanism

Nature, Journal Year: 2016, Volume and Issue: 539(7628), P. 197 - 206

Published: Nov. 8, 2016

Language: Английский

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Amyotrophic Lateral Sclerosis

New England Journal of Medicine, Journal Year: 2017, Volume and Issue: 377(2), P. 162 - 172

Published: July 12, 2017

Progress has been made in understanding the genetic defects and pathophysiology of this crippling motor neuron disease (commonly called Lou Gehrig's disease). However, information not yet led to a successful intervention that alters course disease.

Language: Английский

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State of play in amyotrophic lateral sclerosis genetics

Nature Neuroscience, Journal Year: 2013, Volume and Issue: 17(1), P. 17 - 23

Published: Dec. 26, 2013

Language: Английский

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Amyotrophic lateral sclerosis

Nature Reviews Disease Primers, Journal Year: 2017, Volume and Issue: 3(1)

Published: Oct. 5, 2017

Language: Английский

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The changing scene of amyotrophic lateral sclerosis

Nature reviews. Neuroscience, Journal Year: 2013, Volume and Issue: 14(4), P. 248 - 264

Published: March 6, 2013

Language: Английский

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Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Journal Year: 2017, Volume and Issue: 18(3-4), P. 153 - 174

Published: Jan. 5, 2017

This article presents the revised consensus criteria for diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop dementia (FTD) and ALS held London, Canada June 2015. Since publication Strong criteria, there have been considerable advances understanding neuropsychological profile patients with ALS. Not only is breadth depth findings broader than previously recognised - including deficits social cognition language but mixed may also occur. Evidence now shows that are extremely heterogeneous, affecting over 50% persons When present, these significantly adversely impact patient survival. It recognition this clinical heterogeneity association neuroimaging, genetic neuropathological has led to current re-conceptualisation fall along a spectrum. These expand upon those 2009 embrace concept spectrum disorder (ALS-FTSD).

Language: Английский

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Rare-disease genetics in the era of next-generation sequencing: discovery to translation

Nature Reviews Genetics, Journal Year: 2013, Volume and Issue: 14(10), P. 681 - 691

Published: Sept. 3, 2013

Language: Английский

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ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: Dec. 6, 2019

The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with disease risk and pathogenesis, cellular processes involved, grow. Despite decades intense research over 50 potentially causative or disease-modifying identified, etiology remains unexplained treatment options remain limited for majority ALS patients. Various factors have contributed slow progress in understanding developing therapeutics this disease. Here we review genetic basis ALS, highlighting that elusiveness heritability. most commonly mutated ALS-linked are reviewed an emphasis on disease-causing mechanisms. involved pathogenesis discussed, evidence implicating their involvement summarized. Past present therapeutic strategies benefits limitations model systems available researchers discussed future directions may lead effective outlined.

Language: Английский

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Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis

Frontiers in Molecular Neuroscience, Journal Year: 2019, Volume and Issue: 12

Published: Feb. 14, 2019

TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA involved in RNA-related metabolism. Hyper-phosphorylated and ubiquitinated TDP-43 deposits as inclusion bodies the brain spinal cord of patients with motor neuron diseases: amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD). While majority ALS cases (90-95%) are sporadic (sALS), among familial 5-10% involve inheritance mutations TARDBP gene remaining due to other genes such as: C9ORF72, SOD1, FUS, NEK1 etc. Strikingly however, (up 97%) also contain deposited neuronal inclusions, which suggests its pivotal role pathology. Thus, unravelling molecular mechanisms pathology, seems central therapeutics, hence, we comprehensively review current understanding TDP-43's pathology ALS. We discuss roles mutations, cytoplasmic mis-localization aberrant post-translational modifications Also, evaluate amyloid-like vitro aggregation, physiological versus pathological oligomerization vivo, liquid-liquid phase separation (LLPS), potential prion-like propagation propensity inclusions. Finally, describe various evolving TDP-43-induced toxicity impairment endocytosis mitotoxicity emerging strategies towards disaggregation therapeutics.

Language: Английский

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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Neuron, Journal Year: 2018, Volume and Issue: 97(6), P. 1267 - 1288

Published: March 1, 2018

Language: Английский

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