GBA Variants and Parkinson Disease: Mechanisms and Treatments

The GBA gene encodes for the lysosomal enzyme glucocerebrosidase (GCase), which maintains glycosphingolipid homeostasis. Approximately 5–15% of PD patients have mutations in the GBA gene, making it numerically the most important genetic risk factor for Parkinson disease (PD). Clinically, GBA-associated PD is identical to sporadic PD, aside from the earlier age at onset (AAO), more frequent cognitive impairment and more rapid progression. Mutations in GBA can be associated with loss- and gain-of-function mechanisms. A key hallmark of PD is the presence of intraneuronal proteinaceous inclusions named Lewy bodies, which are made up primarily of alpha-synuclein. Mutations in the GBA gene may lead to loss of GCase…

• MJ
  Michael J. Fox Foundation for Parkinson's Research

  Award: ASAP-000420
• EJ
  EU Joint Programme – Neurodegenerative Disease Research

  Award: MR/T046007/1
• AS
  Aligning Science Across Parkinson’s

  Award: ASAP-000420
• NI
  National Institute for Health and Care Research
• UC
  University College London
• MR
  Medical Research Council

  Awards: MR/T046007/1, MR/T046007/1