SRY: A Risk Factor for Parkinson’s disease in Males?

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder, triggered by the death of dopamine neurons in the brain region known as the substantia nigra. Whilst the mechanisms underlying dopamine cell loss in PD, it is clear that males are more susceptible to PD than females. We have identified that the male sex-determining gene SRY directs a novel genetic mechanism of dopamine cell death in males. Understanding when and how SRY increases the vulnerability of male dopamine neurons to injury will help explain why males are more susceptible to the PD and to identify SRY as a novel target for neuroprotective therapy in male PD patients. 1. Lee J, Pinares-Garcia P, Loke H, Ham S, Vilain E,Harley V (2019) Sex-specific neuroprotection by inhibition of the Y-chromosome gene, SRY, in experimental Parkinson’s disease. PNAS 116(33):16577-16582.