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Microglia programmed cell death in neurodegenerative diseases and CNS injury
Ling Cai1, Qiuyue Fan1, Rui Pang1
1Department of Anesthesiology, Key Laboratory of the Ministry of Education, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Programmed cell death (PCD) has emerged as a critical regulatory mechanism in the initiation and progression of various pathological conditions. PCD in microglia, including necroptosis, pyroptosis, apoptosis, ferroptosis, and autophagy, occurs in a variety of central nervous system (CNS) diseases. Dysregulation of microglia can lead to excessive tissue damage or neuronal death in CNS injury. Various injury stimuli trigger aberrant activation of the PCD pathway of microglia, which then further leads to inflammatory cascades that exacerbates CNS pathology in a vicious cycle. Therefore, targeting PCD in microglia is considered an important avenue for the treatment of various neurodegenerative diseases and CNS injury. In this review, we summarize the major and recent findings focusing on the mechanisms of PCD in microglia modulating functions in neurodegenerative diseases and CNS injury and provide a systematic overview of the current inhibitors targeting various PCD pathways, which may provide important therapeutic targets that merit further investigation.
Insights
Programmed cell death (PCD) in microglia plays a key role in central nervous system (CNS) diseases. Targeting microglial PCD pathways offers potential therapeutic strategies for neurodegenerative diseases and CNS injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Programmed cell death (PCD) is a critical regulator in disease pathogenesis.
- Microglia, the immune cells of the central nervous system (CNS), undergo various PCD pathways (necroptosis, pyroptosis, apoptosis, ferroptosis, autophagy) in CNS diseases.
- Dysregulated microglial PCD contributes to neuronal damage and exacerbates CNS pathology through inflammatory cascades.
Purpose of the Study:
- To review the mechanisms of PCD in microglia and their role in neurodegenerative diseases and CNS injury.
- To provide a systematic overview of current inhibitors targeting microglial PCD pathways.
Main Methods:
- Literature review of recent findings on microglial PCD mechanisms.
- Analysis of therapeutic targets and inhibitors for various PCD pathways.
Main Results:
- Microglial PCD is implicated in the initiation and progression of CNS pathologies.
- Aberrant activation of microglial PCD pathways amplifies inflammation and tissue damage.
- Several inhibitors targeting different PCD pathways have been identified.
Conclusions:
- Targeting microglial PCD is a promising therapeutic strategy for CNS diseases.
- Further investigation of these inhibitors may lead to novel treatments for neurodegenerative diseases and CNS injury.
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