Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson's disease.

ABSTRACT: Presynaptic accumulation of misfolded α-synuclein (α-syn) and altered synaptic transmission are considered early events in the pathogenesis of Parkinson's disease (PD), suggesting a potential causal link between these two events. However, the mechanisms by which α-syn aggregation induces synaptic dysfunction and the subsequent progressive neurodegeneration remain elusive. In the present study we leveraged the high temporal resolution of the Light-Inducible Protein Aggregation (LIPA) system in vivo and in human dopaminergic neurons to explore the early sequence of α-syn-induced pathological events leading to synaptopathy. We observed that nigrostriatal axonal transport and presynaptic accumulation of α-syn aggregates altered the activity of different neuronal populations in the mouse striat

SUBMITTER: Rodriguez-Aller R 

PROVIDER: S-EPMC12738572 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature