Signal Transduction and Targeted Therapy· 2023Q1
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
- 1,436citations
- Q1SCImago
- 2023year
Short summary
Reactive microglia exhibit spatial and temporal heterogeneity, with some states correlating with disease hallmarks and specific functions, and can be both protective (phagocytosis) and detrimental (neuroinflammation).
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Key points
- Microglia activation is a hallmark of neurodegenerative diseases, exhibiting complex spatial and temporal heterogeneity.
- Reactive microglia can be both protective (clearing aggregates) and detrimental (causing inflammation and impaired phagocytosis).
- Peripheral immune cell infiltration and microglial extracellular vesicles contribute to disease progression.
- Therapeutic strategies focus on enhancing microglial phagocytosis, reducing neuroinflammation, and promoting protective phenotypes.
AI-generated from the title and abstract; the full text is not read.
Abstract
Microglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington's disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.
The authors' abstract, as published at the source. Signal Transduction and Targeted Therapy, 2023 · DOI ↗
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Field: Neurology (Neuroscience)
NeurologyNeuroscience