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Diversity of Microglia-Derived Molecules with Neurotrophic Properties That Support Neurons in the Central Nervous
Kennedy R Wiens1, Naved Wasti1, Omar Orlando Ulloa1
1Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia, Okanagan Campus, Kelowna, BC V1V 1V7, Canada.
Abstract:
Microglia, the brain immune cells, support neurons by producing several established neurotrophic molecules including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Modern analytical techniques have identified numerous phenotypic states of microglia, each associated with the secretion of a diverse set of substances, which likely include not only canonical neurotrophic factors but also other less-studied molecules that can interact with neurons and provide trophic support. In this review, we consider the following eight such candidate cytokines: oncostatin M (OSM), leukemia inhibitory factor (LIF), activin A, colony-stimulating factor (CSF)-1, interleukin (IL)-34, growth/differentiation factor (GDF)-15, fibroblast growth factor (FGF)-2, and insulin-like growth factor (IGF)-2. The available literature provides sufficient evidence demonstrating murine cells produce these cytokines and that they exhibit neurotrophic activity in at least one neuronal model. Several distinct types of neurotrophic activity are identified that only partially overlap among the cytokines considered, reflecting either their distinct intrinsic properties or lack of comprehensive studies covering the full spectrum of neurotrophic effects. The scarcity of human-specific studies is another significant knowledge gap revealed by this review. Further studies on these potential microglia-derived neurotrophic factors are warranted since they may be used as targeted treatments for diverse neurological disorders.
Insights
Microglia secrete various neurotrophic factors beyond known ones, including eight candidate cytokines with neurotrophic activity in mice. Further research is needed to explore their therapeutic potential for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, are known to produce neurotrophic factors like glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF).
- Recent advancements reveal diverse microglial phenotypes secreting various substances, potentially including novel neurotrophic molecules.
- This review focuses on eight candidate cytokines with potential neurotrophic roles: oncostatin M (OSM), leukemia inhibitory factor (LIF), activin A, colony-stimulating factor (CSF)-1, interleukin (IL)-34, growth/differentiation factor (GDF)-15, fibroblast growth factor (FGF)-2, and insulin-like growth factor (IGF)-2.
Purpose of the Study:
- To review the neurotrophic potential of eight candidate cytokines secreted by microglia.
- To identify distinct neurotrophic activities and knowledge gaps regarding these factors.
- To highlight the need for further research into microglia-derived neurotrophic factors for therapeutic applications.
Main Methods:
- Literature review of studies investigating the production and neurotrophic activity of the selected eight cytokines.
- Analysis of existing evidence for neurotrophic effects in at least one neuronal model, primarily focusing on murine studies.
- Identification of overlapping and distinct neurotrophic activities among the studied cytokines.
Main Results:
- Sufficient evidence demonstrates that murine cells produce these eight cytokines and that they exhibit neurotrophic activity in various neuronal models.
- Distinct neurotrophic activities were identified, with partial overlap among the cytokines, suggesting unique intrinsic properties or incomplete characterization.
- A significant knowledge gap exists regarding human-specific studies for these potential neurotrophic factors.
Conclusions:
- The eight reviewed cytokines represent potential microglia-derived neurotrophic factors with demonstrated activity in preclinical models.
- Understanding the specific neurotrophic roles of these cytokines is crucial for developing targeted therapies.
- Further investigation, particularly in human systems, is warranted to explore their therapeutic utility for neurological disorders.
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