Microglia and microglial-based receptors in the pathogenesis and treatment of Alzheimer?s disease

Alzheimer's disease (AD) manifests as progressive deterioration in multiple cognitive and information processing domains, including memory and executive functions. Although AD's cause and cure remain elusive, increasing evidence supports a key role for microglial cells in AD pathogenesis via diverse mechanisms. beta-Amyloid (A beta) and tau triggered proteopathic and immunopathic processes are key contributors to AD pathology. These proteins aggregate into oligomers and fibrils, which eventually deposit in the central nervous system (CNS) as plaques and tangles. A beta and tau are directly synaptotoxic and neurotoxic, but also concomitantly induce neuroinflammation. As a central player in CNS immunity, microglia recognize different forms of misfolded proteins and initiate subsequent immune responses, mediating neuroinflammation and neuron-glia crosstalk. Microglia phagocytose debris and release cytokines to maintain brain homeostasis and synaptic integrity. However, microglia also exhibit harmful effects when subject to prolonged activation. This review describes the role of microglia in the proteopathic-immunopathic pathogeneses of AD. We summarize the microglial receptors involved in A beta recog-nition, and the role played by this interaction in explaining the interplay between A beta accumulation and AD progression through microglia-mediated neuroinflammation. Based on the dual proteopathic and immunopathic roles of microglia, we also review putative drug candidates targeting microglial receptors.

Automated summary

Alzheimer's disease is a neurodegenerative disorder characterized by the progressive deterioration of multiple cognitive functions. Microglial cells play a crucial role in the pathogenesis of Alzheimer's disease through the recognition and response to misfolded proteins like beta-amyloid and tau. These proteins contribute to neuroinflammation and neurotoxicity, while microglia's primary function is to maintain brain homeostasis and synaptic integrity. However, prolonged activation of microglia can be harmful. This review discusses the role of microglia in Alzheimer's disease pathogenesis and explores potential drug candidates targeting microglial receptors.