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

Le résumé fourni par la source

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)

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.