NADPH氧化酶
小胶质细胞
神经炎症
细胞生物学
p38丝裂原活化蛋白激酶
TLR4型
化学
信号转导
激酶
蛋白激酶A
药理学
氧化应激
炎症
生物化学
生物
免疫学
作者
Mark F. McCarty,Aaron Lerner
标识
DOI:10.1080/14737175.2021.1907182
摘要
A delayed second wave of brain trauma is mediated in large part by microglia that are activated to a pro-inflammatory M1 phenotype by DAMP proteins released by dying neurons. These microglia can promote apoptosis or necrosis in neighboring neurons by producing a range of pro-inflammatory cytokines and the deadly oxidant peroxynitrite. This second wave could therefore be mitigated with agents that blunt the post-traumatic M1 activation of microglia and that preferentially promote a pro-healing M2 phenotype.The literature on nutraceuticals that might have clinical potential in this regard.The chief signaling pathway whereby DAMPs promote M1 microglial activation involves activation of toll-like receptor 4 (TLR4), NADPH oxidase, NF-kappaB, and the stress activated kinases JNK and p38. The green tea catechin EGCG can suppress TLR4 expression. Phycocyanobilin can inhibit NOX2-dependent NADPH oxidase, ferulate and melatonin can oppose pro-inflammatory signal modulation by NADPH oxidase-derived oxidants. Long-chain omega-3 fatty acids, the soy isoflavone genistein, the AMPK activator berberine, glucosamine, and ketone bodies can down-regulate NF-kappaB activation. Vitamin D activity can oppose JNK/p38 activation. A sophisticated program of nutraceutical supplementation may have important potential for mitigating the second phase of neuronal death and aiding subsequent healing.
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