Alpha-synuclein pathology in the "weaver" mouse, a genetic model of dopaminergic denervation

Alpha-synuclein plays a pivotal role in Parkinson's disease (PD) pathogenesis, with α-synuclein aggregates/oligomers being identified as toxic species and phosphorylation at Serine 129 promoting aggregation/oligomerization. We investigated the biochemical profile of α-synuclein in the "weaver" mouse, a genetic PD model. Our results revealed increased Serine 129 phosphorylation in the midbrain, striatum, and cortex at a phase of established dopaminergic degeneration on postnatal day 100. These results indicate α-synuclein pathology already at this stage and the potential for age-related progress. Our findings confirm that the "weaver" mouse is an invaluable genetic model to study α-synuclein pathogenesis during PD progression.