Microglia in Alzheimer’s Disease: A Favorable Cellular Target to Ameliorate Alzheimer’s Pathogenesis

Abstract

Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid β phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer’s disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.