Microglial Lag3 Drives α-Synuclein-induced Neurotoxic Activated (A1) Astrocytes and Neurodegeneration.

ABSTRACT:

Background

Neuroinflammation and pathologic α-synuclein (α-syn) aggregation cooperate to drive dopaminergic neurodegeneration in Parkinson's disease, but the glial receptors that couple extracellular α-syn to inflammatory cascades remain incompletely defined. Microglia express higher levels of lymphocyte activation gene 3 (Lag3) than neurons, yet the contribution of microglial Lag3 to α-syn recognition, glial crosstalk, and neurodegeneration is unknown.

Methods

Biochemical binding assays, live-cell imaging, cytokine profiling, and neuron-microglia-astrocyte co-culture paradigms were used to define Lag3-dependent α-syn preformed fibril (PFF) binding, uptake, and microglial activation. To interrogate in vivo function, microglia-specific Lag3 conditional knockout mice (Lag3

SUBMITTER: Yang X 

PROVIDER: S-EPMC12803170 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature