Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis.

Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis.
Neurobiol Dis. 2020 Oct 31;:105144
Authors: Ugbode C, West RJH
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.
PMID: 33144171 [PubMed - as supplied by publisher]

Source: Neurobiology of Disease - October 31, 2020 Category: Neurology Authors: Ugbode C, West RJH Tags: Neurobiol Dis Source Type: research