Mechanism of microglia-mediated neuroinflammation, associated cognitive dysfunction, and therapeutic updates in Alzheimer's disease

Alzheimer's disease (AD) and associated cognitive dysfunction are major healthcare challenges globally. Various mechanisms of pathogenesis and signaling molecules have been studied for their plausible role in disease initiation and progression. Neuroinflammation has been considered a major hallmark of AD. Amyloid beta (Aβ), hyperphosphorylated tau protein, and formed neurofibrillary tangles (NFT) are positively correlated with neuroinflammation. Microglial activation was found to be a key contributor to neuroinflammation, AD pathogenesis, and progression. The mechanism of microglial activation has been studied in detail, and looking into its pivotal role in disease etiology, various drugs have been developed, and many are in the clinical phases of development. These drugs either inhibit the microglial activation or neuroinflammatory event postmicroglial activation. Considering these facts, in the present study, we herein discuss the mechanism of microglial activation and the mechanism of neuroinflammation related to microglial activation and dementia. Here we also discussed the various drugs that either act at tau protein or mitigate neuroinflammation, along with their status in clinical trials. In brief, this review provides an in-depth mechanism of microglial activation and updates on drugs that can inhibit this activation, leading to significant anti-Alzheimer effect and mitigation of cognitive dysfunction. • Microglial activation has a significant impact on the pathogenesis of Alzheimer's disease. • Understanding the molecular mechanism of microglial activation is important to design, develop, or repurpose the drugs. • Various natural products or small molecules have shown a significant positive impact on microglial-activated Alzheimer's disease. • Various clinical trials are under different phases, and in the coming time, drugs might change the landscape of Alzheimer's disease treatment.