Interaction between extracellular ATP5A1 and LPS alleviates LPS-induced neuroinflammation in mice

Abstract

Neuroinflammation is one of the main causes of Alzheimer’s disease (AD). The presence of Lipopolysaccharide (LPS) in senile plaques (SP) of AD suggests that it plays a role in AD pathogenesis. ATP5A1 (F1F0-ATP synthase F1 α subunit) is abundant in SP. Further, the protein has recently been found to have an anti-infection role in zebrafish embryos. In the present study, we observed that LPS levels were higher in the brains of APP/PS1 mice than in control mice, and LPS co-localised with ATP5A1 in amyloid plaques. The interaction of recombinant ATP5A1(rATP5A1) and LPS was evidenced by cellular thermal shift assay and enzyme-linked immunosorbent assay-based binding assay in vitro. Neuroinflammation in the brain of a mouse model was induced by intracerebroventricular injection of LPS. The addition of rATP5A1 relieved LPS-induced reduction of spontaneous locomotor ability, depressive-like behaviour, and working memory impairment. Furthermore, rATP5A1 suppressed the activation of astrocytes and microglia, IL-1β accumulation, and tau phosphorylation induced by LPS. Taken together, findings suggest that ATP5A1 is involved in the regulation of LPS-mediated neuroinflammation in AD.