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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.