Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls.
E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease.
Here, we used an αS tetramer-abrogating mouse model of PD (3K) that amplifies the familial E46KPD mutation to investigate the effects of female sex and brain-selective estrogen treatment on αS tetramerization and solubility, formation of vesicle-rich αS<sup>+</sup> aggregates, dopaminergic and cortical fiber integrity, and associated motor deficits.