Abstract
Microglia often accumulate around degenerating neurons. These macrophage-like immune cells produce a variety of neurotoxic and neuroprotective factors. Thus, the accumulation of glia in various neurologic disorders does not reflect only gliosis, but likely results in an active contribution to neuroinflammation, neural degeneration, and cell regeneration. We previously showed that glutamate is the most neurotoxic factor released by activated microglia, and suppressing glutamate release from microglia can inhibit disease progression in various animal models of neurodegenerative disorders. Interferon-γ (IFNγ) is also neurotoxic after binding to IFNγ receptor alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor complexes. On the other hand, when exposed to harmful stimuli, neurons also produce and release various factors that serve as “help-me” signals. For example, the CX3C chemokine fractalkine, interleukin-34, and fibroblast growth factor-2 are secreted from damaged neurons; these help-me signals induce various microglial activities to rescue neurons, including upregulated phagocytosis of toxicants and damaged debris, and production of antioxidant enzymes and other neurotrophic factors. Elucidating the interactions between neurons and microglia will help uncover the mechanisms underlying chronic neuroinflammatory conditions, and may provide insights into new therapeutic strategies for neurodegenerative disorders.
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Acknowledgments
This work was supported in part by the Global COE program “Integrated Functional Molecular Medicine for Neuronal and Neoplastic Disorders,” which is funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation (NIBIO).
Conflicts of interest The author has no conflicts of interest to declare.
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Suzumura, A. (2013). Interactions Between Neurons and Microglia During Neuroinflammation. In: Suzumura, A., Ikenaka, K. (eds) Neuron-Glia Interaction in Neuroinflammation. Advances in Neurobiology, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8313-7_4
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DOI: https://doi.org/10.1007/978-1-4614-8313-7_4
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