CD11b Activation Reduces Myeloid Brain Infiltration and Mitigates Synucleinopathy in a Model of Parkinson's Disease.

ABSTRACT: The pathology of Parkinson's disease is defined by α-synuclein (α-syn) aggregation into neuronal Lewy bodies, which may lead to chronic neuroinflammation and dopaminergic neurodegeneration. Misfolded α-syn activates Toll-like receptor signaling in microglia, leading to downstream activation of NF-κB and subsequent release of pro-inflammatory cytokines. These cytokines recruit pro-inflammatory myeloid cells from circulation, thereby amplifying neuroinflammation. Thus, reducing microglial activation and myeloid cell infiltration has the potential to reduce neuroinflammation and PD pathology. Here, we investigated a targeted immunomodulatory strategy using LA1, a novel, small-molecule agonist of CD11b, a β2 integrin receptor highly and selectively expressed on myeloid cells and microglia. CD1

SUBMITTER: Shaw AM 

PROVIDER: S-EPMC12363877 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature