One of the largest unmet medical needs is a disease-modifying treatment for Alzheimer's disease (AD). Recently the role of microglia in disease, particularly AD, has gained great interest, following the identification of several disease risk-associated genes that are highly expressed in microglia. Microglia play a critical homeostatic role in the brain, with neuroinflammatory and phagocytic mechanisms being of particular importance. Here we review the role of NLRP3, the complement system, and TREM2 in modulating microglial functions. Reviewed are the targets, their molecular pathways, and the therapeutic interventions aimed at modulating these targets, in the hope of discovering a novel therapeutic approach for the treatment of AD.
Br J Pharmacol
Alzheimer's disease, Complement, Microglia, NLRP3, Neuroinflammation, Phagocytosis, TREM2