Ugbode, Christopher orcid.org/0000-0002-6023-8294 and West, Ryan John Hatcher (2020) Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiology of disease. 105144. ISSN 1095-953X
Abstract
Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are two neurodegenerative diseases with clinical, genetic and pathological overlap. As such, they are commonly regarded as a single spectrum disorder, with pure FTD and pure ALS representing distinct ends of a continuum. Dysfunctional endo-lysosomal and autophagic trafficking, leading to impaired proteostasis is common across the FTD-ALS spectrum. These pathways are, in part, mediated by CHMP2B, a protein that coordinates membrane scission events as a core component of the ESCRT machinery. Here we review how ALS and FTD disease causing mutations in CHMP2B have greatly contributed to our understanding of how endosomal-lysosomal and autophagic dysfunction contribute to neurodegeneration, and how in vitro and in vivo models have helped elucidate novel candidates for potential therapeutic intervention with implications across the FTD-ALS spectrum.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Neurodegeneration,CHMP2B,Therapeutics,Immunity,Proteostasis,FTD,ALS,ESCRT,Motor Neurone Disease |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Nov 2020 17:30 |
Last Modified: | 20 Dec 2024 00:18 |
Published Version: | https://doi.org/10.1016/j.nbd.2020.105144 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1016/j.nbd.2020.105144 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167560 |