Abstract
Beta-glucocerebrosidase is a lysosomal hydrolase, encoded by GBA1 that represents the most common risk gene associated with Parkinson's disease (PD) and Lewy Body Dementia. Glucocerebrosidase dysfunction has been also observed in the absence of GBA1 mutations across different genetic and sporadic forms of PD and related disorders, suggesting a broader role of glucocerebrosidase in neurodegeneration. In this review, we highlight recent advances in mechanistic characterization of glucocerebrosidase function as the foundation for development of novel therapeutics targeting glucocerebrosidase in PD and related disorders.
| Original language | English (US) |
|---|---|
| Article number | 168023 |
| Journal | Journal of Molecular Biology |
| Volume | 435 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2023 |
Funding
This work was supported by the National Institute of Neurological Disorders and Stroke (D.K. 5R35NS122257). D.C. is supported by a training grant from the National Institute of Aging (T32AG020506). The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.K. is the founder of Vanqua Bio, Lysosomal Therapeutics, Inc. and serves on the Scientific Advisory Board of Intellia Therapeutics, AcureX Therapeutics, Leal Therapeutics, The Silverstein Foundation and serves as a Venture Partner at OrbiMed. This work was supported by the National Institute of Neurological Disorders and Stroke (D.K., 5R35NS122257). D.C. is supported by a training grant from the National Institute of Aging (T32AG020506).
Keywords
- GBA1
- Parkinson's disease
- glucocerebrosidase
- lysosomes
- neurodegeneration
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Molecular Biology