GBA1 mutations: Prospects for exosomal biomarkers in α-synuclein pathologies

Publication date: Available online 23 October 2019Source: Molecular Genetics and MetabolismAuthor(s): Parker Johnson, Neal J. Weinreb, James Cloyd, Paul J. Tuite, Reena V. KarthaAbstractThe discovery that patients with Gaucher Disease (GD), a rare lysosomal storage disorder, were developing symptoms similar to Parkinson's disease (PD) led to investigation of the relationship between the two seemingly unrelated pathologies. GD, an autosomal recessive disorder, is the result of a biallelic mutation in the gene GBA1, which encodes for the enzyme glucocerebrosidase (GCase). Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies. Although the exact mechanism by which GBA1 mutations promote PD is unknown, current understanding suggests that impaired GCase inhibits lysosomal activity and decreases the overall ability of the cell to degrade proteins, specifically the neuronal protein α -synuclein. Decreased elimination of α -synuclein can lead to its abnormal accumulation and aggregation, an important component of PD development. Further understanding of how decreased GCase activity increases risk for α-synuclein pathology can assist with the identification and development of clinical biomarkers for early detection of synucleinopathies, as well as novel treatments tailored for people with a GBA1 mutation. Historically, α-synuclein has no...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research