Abstract | PURPOSE OF REVIEW: GBA1 mutations, which result in the lysosomal disorder Gaucher disease, are the most common known genetic risk factor for Parkinson disease and Dementia with Lewy Bodies (DLB). The pathogenesis of this association is not fully understood, but further elucidation of this link could lead to new therapeutic options. RECENT FINDINGS: SUMMARY: As our understanding of GBA1-associated Parkinson disease increases, new treatment opportunities emerge. MicroRNA profiles are providing examples of both up-regulated and down-regulated proteins related to GBA1 and may provide new therapeutic targets. Chaperone therapy, directed at either misfolded glucocerebrosidase or α- synuclein aggregation, is currently under development and there are several early clinical trials ongoing. Substrate reduction therapy, aimed at lowering the accumulation of metabolic by-products, especially glucosylsphingosine, is also being explored. Basic science insights from the rare disorder Gaucher disease are serving to catapult drug discovery for parkinsonism.
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Authors | Emory Ryan, Gurpreet Seehra, Pankaj Sharma, Ellen Sidransky |
Journal | Current opinion in neurology
(Curr Opin Neurol)
Vol. 32
Issue 4
Pg. 589-596
(08 2019)
ISSN: 1473-6551 [Electronic] England |
PMID | 31188151
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Protein Aggregates
- alpha-Synuclein
- GBA protein, human
- Glucosylceramidase
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Topics |
- Gaucher Disease
(genetics)
- Glucosylceramidase
(genetics, metabolism)
- Humans
- Lewy Body Disease
(genetics, metabolism, therapy)
- Mutation
- Parkinsonian Disorders
(genetics, metabolism, therapy)
- Protein Aggregates
- alpha-Synuclein
(metabolism)
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