Microglial CR3 promotes neuron ferroptosis via NOX2-mediated iron deposition in rotenone-induced experimental models of Parkinson's disease.

ABSTRACT: The activation of complement receptor 3 (CR3) in microglia contributes to neurodegeneration in neurological disorders, including Parkinson's disease (PD). However, it remains unclear for mechanistic knowledge on how CR3 mediates neuronal damage. In this study, the expression of CR3 and its ligands iC3b and ICAM-1 was found to be up-regulated in the midbrain of rotenone PD mice, which was associated with elevation of iron content and disruption of balance of iron metabolism proteins. Interestingly, genetic deletion of CR3 blunted iron accumulation and recovered the expression of iron metabolism markers in response to rotenone. Furthermore, reduced lipid peroxidation, ferroptosis of dopaminergic neurons and neuroinflammation were detected in rotenone-lesioned CR3^-/- mice compared

SUBMITTER: Wang Q 

PROVIDER: S-EPMC11471230 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature