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For a long time, there has been a recognized link between GBA gene sequence variants and risk of Parkinson disease (PD). In fact, Neurology® published an editorial 14 years ago by Rogaeva and Hardy1 on this topic. The GBA gene, also known as glucosylceramidase β, encodes the lysosomal membrane protein called glucocerebrosidase (GCase). GCase is responsible for breaking down the molecule glucosylceramide. GBA gene sequence variants lead to loss of GCase activity, which results in uncontrolled accumulation of glucosylceramide. As a downstream effect, loss of GCase activity has been linked to α-synuclein aggregation, a key pathologic mechanism of PD.2 This suggests that GCase activity may be an important biological factor in PD clinical research.
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.
See page 180
- Received September 13, 2022.
- Accepted in final form October 3, 2022.
- © 2022 American Academy of Neurology
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