Vicious Cycles: Dysfunctional GCase and Parkinson’s Disease
Mutations in the GBA gene are one of the most common genetic factors associated with Parkinson’s disease, yet it is still unknown how the enzyme coded by the gene, glucocerebrosidase (GCase), directly influences pathogenesis. However, recent systematic investigation offers answers regarding the important role GCase may play in the risk factor of developing the disease.
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magine a disease that could strike at any time, where prevention is futile and nearly all cases have an unknown origin or cause. Parkinson’s disease (PD) has a nearly identical epidemiology to this hypothetical disease, and though many breakthroughs in its pathology have occurred over the last 200 years, many of the risk factors and contributors to the development of Parkinson’s disease are still shrouded in mystery. Using a combination of methods, Henderson et al. (2020) explores the complex interactions between the activity of a lysosomal enzyme, GCase, and the accumulation of dangerous forms of α-synuclein, the hallmark indicator of Parkinson’s disease. This proverbial unveiling of the role of GCase activity, and by extension mutations in the GBA1 gene which codes for it, profoundly improve both our understanding of the pathology of parkinsonian diseases and opens the door to future therapeutic targets for treatment.