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

Research output: Contribution to journalReview articlepeer-review


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.
Original languageEnglish
Article number105144
JournalNeurobiology of disease
Early online date2 Nov 2020
Publication statusE-pub ahead of print - 2 Nov 2020


  • Neurodegeneration
  • CHMP2B
  • Therapeutics
  • Immunity
  • Proteostasis
  • FTD
  • ALS
  • Motor Neurone Disease

Cite this