Ugbode, C. and West, R.J.H. orcid.org/0000-0001-9873-2258 (2021) Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiology of Disease, 147. 105144. ISSN 0969-9961
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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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Neurodegeneration; Therapeutics; Immunity; Proteostasis; FTD; ALS; ESCRT; Motor neurone disease; CHMP2B |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Feb 2021 15:29 |
Last Modified: | 01 Feb 2021 15:29 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.nbd.2020.105144 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169790 |