Glucocerebrosidase deficits in sporadic Parkinson disease

Autophagy. 2014 Jul;10(7):1350-1. doi: 10.4161/auto.29074. Epub 2014 May 15.


Parkinson disease (PD) is a progressive neurodegenerative movement disorder characterized pathologically by abnormal SNCA/α-synuclein protein inclusions in neurons. Impaired lysosomal autophagic degradation of cellular proteins is implicated in PD pathogenesis and progression. Heterozygous GBA mutations, encoding lysosomal GBA/glucocerebrosidase (glucosidase, β, acid), are the greatest genetic risk factor for PD, and reduced GBA and SNCA accumulation are related in PD models. Here we review our recent human brain tissue study demonstrating that GBA deficits in sporadic PD are related to the early accumulation of SNCA, and dysregulation of chaperone-mediated autophagy (CMA) pathways and lipid metabolism.

Keywords: Parkinson disease; autophagy; ceramide; chaperone-mediated autophagy; glucocerebrosidase; lysosomes; α-synuclein.

Publication types

  • Review

MeSH terms

  • Autophagy
  • Glucosylceramidase / deficiency*
  • Humans
  • Lipid Metabolism
  • Molecular Chaperones / metabolism
  • Parkinson Disease / enzymology*
  • Parkinson Disease / pathology*
  • alpha-Synuclein / metabolism


  • Molecular Chaperones
  • alpha-Synuclein
  • Glucosylceramidase