MHCII reduction is insufficient to protect mice from alpha-synuclein-induced degeneration and the Parkinson's HLA locus exhibits epigenetic regulation.

ABSTRACT: Major histocompatibility complex class II (MHCII) molecules are antigen presentation proteins and increased in post-mortem Parkinson's disease (PD) brain. Attempts to decrease MHCII expression have led to neuroprotection in PD mouse models. Our group reported that a single nucleotide polymorphism (SNP) at rs3129882 in the MHCII gene Human Leukocyte Antigen (HLA) DRA is associated with increased MHCII transcripts and surface protein and increased risk for late-onset idiopathic PD. We therefore hypothesized that decreased MHCII may mitigate dopaminergic degeneration. During an ongoing α-synuclein lesion, mice with MHCII reduction in systemic and brain innate immune cells (LysMCre + I-Ab^fl/fl or CRE+) displayed brain T cell repertoire shifts and greater preservation of the dopamine

SUBMITTER: Kline EM 

PROVIDER: S-EPMC12012047 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature