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The Dual Nature of Microglia in Alzheimer’s Disease: A Microglia-Neuron Crosstalk Perspective

Xie, Zhen, Meng, Jie, Wu, Zhou, Nakanishi, Hiroshi, Hayashi, Yoshinori, Kong, Wei, Lan, Fei, Narengaowa, Yang, Qinghu, Qing, Hong, Ni, Junjun·2023·The Neuroscientist
DOI 10.1177/10738584211070273
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Abstract

Microglia are critical players in the neuroimmune system, and their involvement in Alzheimer’s disease (AD) pathogenesis is increasingly being recognized. However, whether microglia play a positive or negative role in AD remains largely controversial and the precise molecular targets for intervention are not well defined. This partly results from the opposing roles of microglia in AD pathology, and is mainly reflected in the microglia-neuron interaction. Microglia can prune synapses resulting in excessive synapse loss and neuronal dysfunction, but they can also promote synapse formation, enhancing neural network plasticity. Neuroimmune crosstalk accelerates microglial activation, which induces neuron death and enhances the microglial phagocytosis of β-amyloid to protect neurons. Moreover, microglia have dual opposing roles in developing the major pathological features in AD, such as amyloid deposition and blood-brain barrier permeability. This review summarizes the dual opposing role of microglia in AD from the perspective of the interaction between neurons and microglia. Additionally, current AD treatments targeting microglia and the advantages and disadvantages of developing microglia-targeted therapeutic strategies are discussed.

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Metadata

Authors
Xie, Z., Meng, J., Wu, Z., Nakanishi, H., Hayashi, Y., Kong, W., Lan, F., Narengaowa, Yang, Q., Qing, H., & Ni, J.
Affiliations
  • Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Department of Biology, Beijing Institute of Technology, Beijing, China
  • Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
  • Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
  • Department of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima, Japan
  • Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan
  • Research Center for Resource Peptide Drugs, Shanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, Yanan University, Yanan, China
ORCID
Venue
The Neuroscientist
Publisher
SAGE Publications
Published
2022-03-29
Volume
29
Issue
5
Pages
616-638
ISSN
  • 1073-8584
  • 1089-4098
DOI
10.1177/10738584211070273
Cited by
19
References
57
Language
en
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Funders
  • Beijing Natural Science Foundation (7212066)
  • Organization Department of CPC Yan’an Municipal Committee (203010108)
  • National Natural Science Foundation of China (32070954)
  • Yan’an University (YDBK2019-41)
  • China Postdoctoral Science Foundation (2021M692266)

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