Microglia Phenotypes in Aging and Neurodegenerative Diseases

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Neuroinflammation, driven by microglia, is central to neurodegenerative diseases (NDs).
• Microglia exhibit complex, context-dependent roles, acting as both protective and detrimental forces in disease.
• Chronic microglial activation is observed across various acute and chronic neuropathological conditions.

Purpose of the Study:

• To provide a comprehensive overview of microglial phenotypes and inflammatory responses in health, aging, and NDs.
• To emphasize the heterogeneous microglial responses in conditions like hemorrhagic stroke (HS), Alzheimer's disease (AD), and Parkinson's disease (PD).
• To review potential therapeutic targets for modulating microglial responses.

Main Methods:

• Analysis of translational research in preclinical animal models.
• Examination of bulk and single-cell transcriptome studies from human postmortem samples.
• Review of existing literature on microglial receptors and signaling pathways.

Main Results:

• Microglial responses are heterogeneous and depend on the inflammatory insult's nature, duration, and disease stage.
• Evidence highlights both detrimental and protective microglial phenotypes in pathological conditions.
• Key microglial receptors and signaling pathways are identified as potential therapeutic targets.

Conclusions:

• Understanding microglial heterogeneity is crucial for developing effective therapies for NDs.
• Modulating microglial inflammatory responses offers a promising therapeutic strategy for aging and neurodegeneration.
• Further research into age-, sex-, and species-specific microglial differences is warranted.