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Advanced therapeutic strategies targeting microglia: beyond neuroinflammation
1Department of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA University, CHA BIO COMPLEX, 335 Pangyo, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea. minsoo100@cha.ac.kr.
Abstract:
For a long time, microglia have been recognized as the main culprits of neuroinflammatory responses because they are primary phagocytes present in the parenchyma of the central nervous system (CNS). However, with the evolving concept of microglial biology, advanced and precise approaches, rather than the global inhibition of activated microglia, have been proposed in the management of neurological disorders. Yolk sac-derived resident microglia have heterogeneous composition according to brain region, sex, and diseases. They play a key role in the maintenance of CNS homeostasis and as primary phagocytes. The perturbation of microglia development can induce neurodevelopmental disorders. Microglia aggravate or alleviate neuroinflammation according to microenvironment and their spatiotemporal dynamics. They are long-lived cells and repopulate via their proliferation or external monocyte engraft. Based on this evolving concept, understanding advanced therapeutic strategies targeting microglia can give us an opportunity to discover novel therapies for neurological disorders.
Insights
Microglia, the central nervous system's immune cells, are key to brain health but can also drive neuroinflammation. Targeting specific microglial functions offers new therapeutic avenues for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are recognized as key players in neuroinflammation and central nervous system (CNS) homeostasis.
- Their role is complex, as they can both aggravate and alleviate neuroinflammation depending on context.
Purpose of the Study:
- To explore the evolving understanding of microglial biology and its implications for neurological disorder therapies.
- To highlight the potential of advanced, targeted strategies for managing neurological conditions.
Main Methods:
- Review of current literature on microglial heterogeneity and function.
- Analysis of microglial repopulation mechanisms (proliferation and monocyte engraftment).
Main Results:
- Microglia exhibit regional, sex-based, and disease-specific heterogeneity.
- Perturbations in microglial development are linked to neurodevelopmental disorders.
- Microglial responses are dynamic and influenced by their microenvironment.
Conclusions:
- Global inhibition of microglia is less effective than targeted approaches.
- Understanding microglial spatiotemporal dynamics is crucial for developing novel therapies.
- Targeting microglia presents a promising strategy for treating neurological disorders.
