Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation.

ABSTRACT: Lymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins in Parkinson's disease (PD). This study investigates the role of neuronal LAG3 in mediating the binding, uptake, and propagation of α-synuclein (αSyn) preformed fibrils (PFFs). Using neuronal LAG3 conditional knockout mice and human induced pluripotent stem cells-derived dopaminergic (DA) neurons, we demonstrate that LAG3 expression is critical for pathogenic αSyn propagation. Our results show that the absence of neuronal LAG3 significantly reduces αSyn pathology, alleviates motor dysfunction, and inhibits neurodegeneration in vivo. Electrophysiological recordings revealed that αSyn PFFs induce pronounced neuronal hyperactivity in wild-type (WT) neurons, increasing firing rates

SUBMITTER: Yang X 

PROVIDER: S-EPMC11722393 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature