Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.

ABSTRACT: The abnormal deposition of α-synuclein (α-syn) and neuroinflammation are key features of synucleinopathies. We recently demonstrated that leucine-rich repeat kinase 2 (LRRK2) and nuclear factor of activated T cells 1 (NFAT1) modulate the neurotoxic inflammation in synucleinopathies mediated by microglia. Therefore, we hypothesized that targeting NFAT1 might ameliorate the microglial neurotoxicity in synucleinopathies. Here we utilized 11R-VIVIT, an NFAT1 inhibitory peptide, in in vivo, ex vivo and in vitro synucleinopathy models to evaluate the effects of NFAT1 inhibition to test this hypothesis. The microglia in synucleinopathy mouse models become excessively activated due to chronic disease conditions, thereby increasing the expressions of proinflammatory cytokines in these cells and dec

SUBMITTER: Iba M 

PROVIDER: S-EPMC12686539 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature