Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

Abstract

Alzheimer’s disease (AD) is one of the most common types of age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in the AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation and tau pathology, and impairs microglia-associated mitophagy. Thus, targeting microglia may pave the way for new therapeutic interventions. This review provides a thorough overview of the pathophysiological role of the microglia in AD and illustrates the potential avenues for microglia-targeted therapies, including microglial modification, immunoreceptors, and anti-inflammatory drugs.

The Neuroprotection of Verbascoside in Alzheimer’s Disease Mediated through Mitigation of Neuroinflammation via Blocking NF-κB-p65 Signaling

“…Neuroinflammation is characterized by the activation of astrocytes and microglia. There are two extreme types of activated microglia: the pro-inflammatory M1 subtype (classically activated) and the anti-inflammatory M2 subtype (alternatively activated) [ 43 ]. In our study, VB lessened the production of M1 markers including iNOS, IL-1β, IL-6, and TNF-α [ 44 ].…”

“…However, persistent stimulation caused by Aβ plaques leads to chronic neuroinflammation and increased release of pro-inflammatory factors, such as TNF-α, IL-1β, and IL-6 from the activated microglia, which in turn inhibits the expression levels of SRs. This promotes the aggregation of Aβ plaques that is followed by exacerbation of neuroinflammation and AD pathology [ 43 , 48 , 49 ]. Pro-inflammatory factors secreted by microglia activate astrocytes to produce more pro-inflammatory mediators, causing an amplification of neuroinflammation [ 50 ].…”

Region-Specific Characteristics of Astrocytes and Microglia: A Possible Involvement in Aging and Diseases

“…Aβ plaques are known to cause the chronic activation of microglia [ 177 ]. Chronically activated microglia secrete proinflammatory cytokines, such as interleukin -1α (IL-1α), tumor necrosis factor-α (TNFα), and complement component 1q (C1q), which further activate nearby astrocytes [ 178 , 179 ]. Thus, in AD, reactive astrocytes with different gene expressions, morphologies, and molecular functions are induced by the extrinsic cues from activated microglia.…”

MAVS mediates a protective immune response in the brain to Rift Valley fever virus

“…Microglia, the resident immune cells of the brain, play a key role in bridging innate and adaptive immune responses in the brain [ 19 – 21 ], and depletion of microglia increases susceptibility to multiple viral infections [ 18 , 22 , 23 ]. Although potent immune responses are required for viral control in the brain, limiting inflammation presents a unique immunoregulatory challenge as excessive inflammation can be especially deleterious and promote neurodegenerative diseases such as Parkinson’s [ 24 ] and Alzheimer’s [ 25 ] disease. Thus, investigation of immune responses in the brain presents an opportunity to understand the interaction of processes that hone the correct response to control viral replication without inducing excessive damaging inflammation.…”