The Vesicular Glutamate Transporter Modulates Sex and Region-Specific Differences in Dopaminergic Neuron α-Synuclein Toxicity by Modifying Cytosolic Dopamine Levels.

ABSTRACT: Parkinson's disease disproportionately affects males; however, the cause of this sex difference is unknown. We found that expressing mutant α-synuclein ^A53T in Drosophila dopamine neurons recapitulates the sex differences observed in human Parkinson's disease patients. Male flies exhibited greater age-related motor impairment and more severe dopamine neuron degeneration than females. Selective masculinization of female dopamine neurons via knockdown of the sex determination gene Transformer eliminated the observed sex differences in locomotor ability and neurodegeneration by increasing the severity of motor defects and degeneration in females. Transformer knockdown in dopamine neurons also reduced total vesicular glutamate transporter staining in the brain.

SUBMITTER: Garzillo K 

PROVIDER: S-EPMC12871730 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature