Inhibition of T cell infiltration and soluble TNF signaling is neuroprotective in the alpha-synuclein overexpressing mouse model of Parkinson's disease.

ABSTRACT: Modulating the neuroinflammatory response is an emerging and interesting approach for treating Parkinson's disease (PD). In this study, we used an adeno-associated virus (AAV9) to overexpress alpha-synuclein (αSyn) in the substantia nigra pars compacta of mice, inducing a dopaminergic degeneration in a dose-dependent manner. αSyn overexpression was associated with CD4⁺ T cell infiltration exhibiting a Th1 (IFNγ⁺TNFα⁺) phenotype in the ventral midbrain. In a chronic model induced with a low viral dose, treatment with either fingolimod (FTY720), which prevents T cell infiltration, or XPro1595, a selective inhibitor of soluble TNF signaling, led to improved motor function and resulted in partially protected dopaminergic cell bodies. These effects were not obse

SUBMITTER: Tavira A 

PROVIDER: S-EPMC12606131 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature