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Microglia-derived sEV: Friend or foe in the pathogenesis of cognitive impairment
1Pulmonary and Critical Care Medicine, Heping District, Shenyang City, Liaoning Province, China.
Abstract:
As immune cells, microglia serve a dual role in cognition. Microglia-derived sEV actively contribute to the development of cognitive impairment by selectively targeting specific cells through various substances such as proteins, RNA, DNA, lipids, and metabolic waste. In recent years, there has been an increasing focus on understanding the pathogenesis and therapeutic potential of sEV. This comprehensive review summarizes the detrimental effects of M1 microglial sEV on pathogenic protein transport, neuroinflammation, disruption of the blood-brain barrier (BBB), neuronal death and synaptic dysfunction in relation to cognitive damage. Additionally, it highlights the beneficial effects of M2 microglia on alleviating cognitive impairment based on evidence from cellular experiments and animal studies. Furthermore, since microglial-secreted sEV can be found in cerebrospinal fluid or cross the BBB into plasma circulation, they play a crucial role in diagnosing cognitive impairment. However, using sEV as biomarkers is still at an experimental stage and requires further clinical validation. Future research should aim to explore the mechanisms underlying microglial involvement in various nervous system disorders to identify novel targets for clinical interventions.
Insights
Microglia-derived extracellular vesicles (sEV) impact cognition. Detrimental M1 microglial sEV worsen cognitive impairment, while beneficial M2 microglial sEV show therapeutic potential for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, play a critical role in cognitive function.
- Microglia-derived small extracellular vesicles (sEV) are increasingly recognized for their involvement in neurological processes.
- Understanding the dual role of microglia and their secreted sEV is crucial for addressing cognitive impairment.
Purpose of the Study:
- To review the detrimental and beneficial effects of microglia-derived sEV on cognitive function.
- To explore the potential of microglial sEV in the pathogenesis and treatment of cognitive disorders.
- To evaluate the diagnostic utility of microglial sEV in cerebrospinal fluid and plasma.
Main Methods:
- Comprehensive literature review of cellular experiments and animal studies.
- Analysis of M1 and M2 microglial sEV contributions to neuroinflammation, protein transport, and neuronal function.
- Assessment of microglial sEV presence in biofluids for diagnostic biomarker potential.
Main Results:
- M1 microglial sEV exacerbate cognitive damage by promoting neuroinflammation, disrupting the blood-brain barrier (BBB), and causing neuronal/synaptic dysfunction.
- M2 microglial sEV demonstrate neuroprotective effects, alleviating cognitive impairment.
- Microglial sEV are detectable in cerebrospinal fluid and plasma, suggesting potential as diagnostic biomarkers.
Conclusions:
- Microglial sEV have a significant, dual impact on cognitive health, with M1 promoting damage and M2 offering protection.
- Microglial sEV hold promise as biomarkers for cognitive impairment, though further clinical validation is required.
- Future research should focus on microglial mechanisms to develop novel therapeutic targets for nervous system disorders.
