How brain ‘cleaners’ fail: Mechanisms and therapeutic value of microglial phagocytosis in Alzheimer's disease

Junjun Ni*, Zhen Xie, Zhenzhen Quan, Jie Meng*, Hong Qing*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

Abstract

Microglia are the resident phagocytes of the brain, where they primarily function in the clearance of dead cells and the removal of un- or misfolded proteins. The impaired activity of receptors or proteins involved in phagocytosis can result in enhanced inflammation and neurodegeneration. RNA-seq and genome-wide association studies have linked multiple phagocytosis-related genes to neurodegenerative diseases, while the knockout of such genes has been demonstrated to exert protective effects against neurodegeneration in animal models. The failure of microglial phagocytosis influences AD-linked pathologies, including amyloid β accumulation, tau propagation, neuroinflammation, and infection. However, a precise understanding of microglia-mediated phagocytosis in Alzheimer's disease (AD) is still lacking. In this review, we summarize current knowledge of the molecular mechanisms involved in microglial phagocytosis in AD across a wide range of pre-clinical, post-mortem, ex vivo, and clinical studies and review the current limitations regarding the detection of microglia phagocytosis in AD. Finally, we discuss the rationale of targeting microglial phagocytosis as a therapeutic strategy for preventing AD or slowing its progression.

Original languageEnglish
Pages (from-to)227-244
Number of pages18
JournalGLIA
Volume72
Issue number2
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Alzheimer's disease
  • microglia
  • phagocytosis
  • therapeutic targets

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Ni, J., Xie, Z., Quan, Z., Meng, J., & Qing, H. (2024). How brain ‘cleaners’ fail: Mechanisms and therapeutic value of microglial phagocytosis in Alzheimer's disease. GLIA, 72(2), 227-244. https://doi.org/10.1002/glia.24465