Journal Article

Microglia in the Neuroinflammatory Pathogenesis of Alzheimer’s Disease and Related Therapeutic Targets

Liu, Jingliu, Sun, Miao, Yang, Hao, Cai, Yongle, Wang, Bin

2022

Overview

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, characterized by progressive neuron degeneration or loss due to excessive accumulation of β-amyloid (Aβ) peptides, formation of neurofibrillary tangles (NFTs), and hyperphosphorylated tau. The treatment of AD has been only partially successful as the majority of the pharmacotherapies on the market may alleviate some of the symptoms. In the occurrence of AD, increasing attention has been paid to neurodegeneration, while the resident glial cells, like microglia are also observed. Microglia, a kind of crucial glial cells associated with the innate immune response, functions as double-edge sword role in CNS. They exert a beneficial or detrimental influence on the adjacent neurons through secretion of both pro-inflammatory cytokines as well as neurotrophic factors. In addition, their endocytosis of debris and toxic protein like Aβ and tau ensures homeostasis of the neuronal microenvironment. In this review, we will systematically summarize recent research regarding the roles of microglia in AD pathology and latest microglia-associated therapeutic targets mainly including pro-inflammatory genes, anti-inflammatory genes and phagocytosis at length, some of which are contradictory and controversial and warrant to further be investigated.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Alzheimer Disease - drug therapy / Alzheimer Disease - etiology / Alzheimer Disease - metabolism / Alzheimer's disease / Amyloid beta-Peptides - metabolism / anti-neuroinflammation / Cytokines / Dementia / Disease / Drugs / Endocytosis / Glial cells / Homeostasis / Humans / Immune response / Immunology / Inflammation / Innate immunity / Kinases / Medical research / Memory / Microenvironments / Microglia / Microglia - metabolism / microglial cells / molecular therapy / Morphology / Neurodegeneration / Neurodegenerative diseases / Neurodegenerative Diseases - metabolism / Neurofibrillary tangles / neuroinflammation / Neuronal-glial interactions / Neurons / Neurons - metabolism / Neurotrophic factors / Pathogenesis / Pathogens / Pathology / Phagocytosis / Proteins / Tau protein / Therapeutic targets / Tissues / β-Amyloid