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

Abstract

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.

From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders

“…Glia cells play a significant role in neurological diseases ( Zhang et al, 2021 ; Cai et al, 2022 ; Rauf et al, 2022 ). Microglia can release large amounts of COX-2 after being stimulated by inflammatory substances.…”

“…Glia cells play a significant role in neurological diseases (Zhang et al, 2021;Cai et al, 2022;Rauf et al, 2022).…”

Microglia dynamics in aging-related neurobehavioral and neuroinflammatory diseases

“…Overall, even though there are many plaque-related microglia in the CNS of AD cases as well as in preclinical models of AD, microglia cannot adequately clear Aβ deposits. Interestingly, microglia could be triggered to do so by Aβ immunotherapy/vaccines attributable to anti-Aβ antibody triggering of IgG receptor (FcR)-regulated phagocytic clearing of Aβ plaques [ 164 , 165 ].…”

Anti-inflammatory activity of Kyungok-go on Lipopolysaccharide-Stimulated BV-2 Microglia Cells

“…In addition, it is known that the microglia could maintain normal brain functions, including the overall structure, the neurotransmitters, and the neuronal synapses 3) . However, upon the microglia is over-activated, Anti-inflammatory activity of Kyungok-go on Lipopolysaccharide-Stimulated BV-2 Microglia Cells microglia produces a large amount of pro-inflammatory cytokines and chemokines, which lead to demyelination, synaptic remodeling, and neuronal death, and ultimately result in the neurodegenerative disease such as Alzheimer's dementia and Parkinson's diseases 4) . Thus, many researches on the regulation of microglia are receiving a lot of attentions as it can contribute to the treatment of neurological diseases.…”

“…Medicine 2022;43(4) are wind (風), fire (火), phlegm (痰), stasis (瘀), and empty (虛), and clinical types can be classified into yin deficiency of liver and kidney (肝腎陰虛), deficiency of energy and blood (氣血 兩虛), phlegm-heat internal damping (痰熱內阻), and stagnation of energy and blood (氣滯血瘀)12) . Therefore, we could hypothesis that the main symptoms of degenerative neurological diseases caused by deficiency and fatigue (虛勞) such as yin deficiency of liver and kidney (肝腎陰虛), and deficiency of energy and blood (氣血兩虛) would be treated by KOG, which can improve deficiency and fatigue (虛勞).…”