Age-dependent progression from clearance to vulnerability in the early response of periventricular microglia to α-synuclein toxic species.

ABSTRACT: Cytoplasmic alpha-synuclein (αSyn) aggregates are a typical feature of Parkinson's disease (PD). Extracellular insoluble αSyn can induce pathology in healthy neurons suggesting that PD neurodegeneration may spread through cell-to-cell transfer of αSyn proteopathic seeds. Early pro-homeostatic reaction of microglia to toxic forms of αSyn remains elusive, which is especially relevant considering the recently uncovered microglial molecular diversity. Here, we show that periventricular microglia of the subependymal neurogenic niche monitor the cerebrospinal fluid and can rapidly phagocytize and degrade different aggregated forms of αSyn delivered into the lateral ventricle. However, this clearing ability worsens with age, leading to an increase in microglia with aggregates in aged treated mice

SUBMITTER: Sirerol-Piquer MS 

PROVIDER: S-EPMC11881471 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature