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Microglial phagoptosis in development, health, and disease
Yuxuan Li1, Shengbo Chen2, Yi-Jun Liu1
1Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Hangzhou 310058, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou 311121, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
Abstract:
Microglial phagoptosis, defined as the phagocytosis of a viable cell by microglia that ultimately causes the death of the engulfed cell, has emerged as a pivotal process in sculpting neural circuits within the central nervous system (CNS). Essential for neurodevelopmental circuit refinement and ongoing tissue homeostasis, this process relies on dynamic molecular cues that direct microglia to specific cellular substrates. Physiologically, phagoptosis contributes to neural circuit refinement and cell number regulation during development; however, its dysregulation can drive neurodevelopmental and neurodegenerative disorders via aberrant cell removal. Recent advances have elucidated the distinct signaling pathways involved in target recognition and engulfment, revealing the dual roles of microglial phagoptosis in both CNS health and disease. Deeper mechanistic insight into this process offers new therapeutic opportunities for conditions characterized by defective or excessive cell clearance. This review summarizes current progress, highlights unresolved challenges, and discusses future perspectives on targeting microglial phagoptosis for intervention in CNS disorders.
Insights
Microglial phagoptosis, the engulfment of viable cells by microglia, is crucial for brain development and health. Its dysregulation contributes to neurological disorders, offering therapeutic targets for CNS conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglial phagoptosis is vital for sculpting neural circuits in the central nervous system (CNS).
- This process is essential for neurodevelopmental refinement and maintaining tissue homeostasis.
- Dysregulation of microglial phagoptosis is implicated in neurodevelopmental and neurodegenerative disorders.
Purpose of the Study:
- To review the current understanding of microglial phagoptosis in the CNS.
- To elucidate the molecular mechanisms underlying microglial target recognition and engulfment.
- To discuss the therapeutic potential of targeting microglial phagoptosis for CNS disorders.
Main Methods:
- Literature review of recent advances in microglial phagoptosis research.
- Analysis of signaling pathways involved in microglial engulfment.
- Discussion of the dual roles of phagoptosis in CNS health and disease.
Main Results:
- Microglial phagoptosis plays critical roles in neural circuit refinement and cell number regulation.
- Distinct molecular cues guide microglia to specific cellular targets.
- Aberrant cell removal via phagoptosis contributes to neurological diseases.
Conclusions:
- Microglial phagoptosis has dual roles in CNS health and disease.
- Understanding the mechanisms of phagoptosis offers therapeutic opportunities.
- Targeting microglial phagoptosis presents a promising strategy for treating CNS disorders.
