Effects of the Antiretroviral Raltegravir on Amyloid-Beta1-42-Induced Neuroinflammation 2310253

Introduction There is growing evidence supporting the potential role of microbial infections in the aetiology of Alzheimer’s disease (AD). We aim to evaluate the effect of raltegravir, either alone as a single therapy or combined with elacridar, a P-gp/BCRP inhibitor, on AD-related pathways in vitro. Methods Flow cytometry combined was used to quantify the expression of key inflammatory markers, including interleukin-1β (IL-1β), NLRP3 inflammasome components, costimulatory molecules (CD86), and the class B scavenger receptor (SR-B2) CD163, in HMC3 human microglia cells. Furthermore, the effect of raltegravir on Aβ1-42-induced p-tau 181 expression in H4 human neuroglioma cells was assessed. Results Results. Our data indicate that raltegravir significantly (p < 0.01) abolishes the Aβ1-42-stimulating effect on p-tau 181, and that this effect involves the downregulation of PP2Aα+β. The observed reduction of p-tau 181 by raltegravir is potentially mediated by the inhibition of tau-phosphatases. Aβ1-42 significantly upregulated the expression of the surface receptors CD86 and CD163 in HMC3 microglial cells. Raltegravir treatment significantly reduced CD86 expression, while it had no significant effect on Aβ1-42-induced CD163 expression (p > 0.05). Further,raltegravir significantly (p < 0.05) attenuated IL-1β cytokine release, likely via downregulation of NLRP3-inflammasome signalling pathway in microglia. Conclusion Taken together, our findings suggest that raltegravir exerts a neuroprotective effect by targeting pathological events associated with AD, particularly tau phosphorylation and neuroinflammation.