Anti-viral immunity induces pS129 alpha synuclein expression independent of alpha synuclein aggregation 4176

Abstract Description Parkinson’s Disease (PD) affects over 10 million people globally, with its prevalence increasing. A hallmark of PD is the aggregation of phosphorylated alpha-synuclein (pS129-Asyn), which is associated with beta-sheet structures. Alpha-synuclein (Asyn), a 140-amino acid protein expressed in neurons, is implicated in PD, but its function and the role of post-translational modifications like pS129-Asyn are not well understood. Our previous research and others showed that Asyn protects neurons from neurotropic viruses and plays a role in immune responses in the enteric and central nervous systems (CNS). We found that Asyn localizes with Stat proteins in neurons during type 1 interferon (T1 IFN) signaling to facilitate interferon-stimulated gene (ISG) expression, whereas IFN signaling was impaired in Asyn knockout neurons. In this study, we interrogated how anti-viral immunity affects Asyn modifications in neurons. We observed that acute viral infection increased Asyn and pS129-Asyn levels in mouse neurons, but did not cause Asyn aggregation. Additionally, in patients with viral encephalitis, pS129-Asyn was elevated and localized to the nucleus of neurons. Neurons treated with Poly I:C or T1 IFN had elevated pS129 levels, but did not lead to Asyn aggregation. Treatment with T1 IFN resulted in nuclear localization of pS129 Asyn. These findings highlight the role of anti-viral immunity in Asyn phosphorylation and may contribute to understanding the early events in PD pathogenesis. Topic Categories Neuroimmunology (NEUR)