Affordable Access

deepdyve-link
Publisher Website

Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing.

Authors
  • Cullen, Valerie
  • Sardi, S Pablo
  • Ng, Juliana
  • Xu, You-Hai
  • Sun, Ying
  • Tomlinson, Julianna J
  • Kolodziej, Piotr
  • Kahn, Ilana
  • Saftig, Paul
  • Woulfe, John
  • Rochet, Jean-Christophe
  • Glicksman, Marcie A
  • Cheng, Seng H
  • Grabowski, Gregory A
  • Shihabuddin, Lamya S
  • Schlossmacher, Michael G
Type
Published Article
Journal
Annals of Neurology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 01, 2011
Volume
69
Issue
6
Pages
940–953
Identifiers
DOI: 10.1002/ana.22400
PMID: 21472771
Source
Medline
License
Unknown

Abstract

Our results demonstrate that GBA mutants promote SNCA accumulation in a dose- and time-dependent manner, thereby identifying a biochemical link between GBA1 mutation carrier status and increased synucleinopathy risk. In cell culture models, this gain of toxic function effect can be mitigated by rapamycin. Loss in GCase activity did not immediately raise SNCA concentrations, but first led to neuronal ubiquitinopathy and axonal spheroids, a phenotype shared with other lysosomal storage disorders.

Report this publication

Statistics

Seen <100 times