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Microglial polarization: novel therapeutic mechanism against Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease that results in progressive dementia, and exhibits high disability and fatality rates. Recent evidence has demonstrated that neuroinflammation is critical in the pathophysiological processes of AD, which is characterized by the activation of microglia and astrocytes. Under different stimuli, microglia are usually activated into two polarized states, termed the classical ‘M1’ phenotype and the alternative ‘M2’ phenotype. M1 microglia are considered to promote inflammatory injury in AD; in contrast, M2 microglia exert neuroprotective effects. Imbalanced microglial polarization, in the form of excessive activation of M1 microglia and dysfunction of M2 microglia, markedly promotes the development of AD. Furthermore, an increasing number of studies have shown that the transition of microglia from the M1 to M2 phenotype could potently alleviate pathological damage in AD. Hence, this article reviews the current knowledge regarding the role of microglial M1/M2 polarization in the pathophysiology of AD. In addition, we summarize several approaches that protect against AD by altering the polarization states of microglia. This review aims to contribute to a better understanding of the pathogenesis of AD and, moreover, to explore the potential of novel drugs for the treatment of AD in the future.

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Acknowledgements

The study was supported by research grants from Research Project of Jinshan District Health and Family Planning Commission (No. JSKJ-KTMS-2018-19), Qi Hang project of Jinshan Hospital (No. 2018-JSYYQH-06). We thank LetPub (https://www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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KY was responsible for the design and manuscript drafting. HZ contributed to figure generation and manuscript writing. All authors read and approved the final manuscript.

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Correspondence to Heng-bing Zu.

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Yao, K., Zu, Hb. Microglial polarization: novel therapeutic mechanism against Alzheimer’s disease. Inflammopharmacol 28, 95–110 (2020). https://doi.org/10.1007/s10787-019-00613-5

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Keywords

  • Alzheimer’s disease
  • Microglia
  • Inflammation
  • Inflammatory signalling pathway
  • NF-κB