Critical role of the Mac1/NOX2 pathway in mediating reactive microgliosis-generated chronic neuroinflammation and progressive neurodegeneration.
Critical role of the Mac1/NOX2 pathway in mediating reactive microgliosis-generated chronic neuroinflammation and progressive neurodegeneration.
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DOI：
10.1016/j.coph.2015.10.001
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发表时间：
2016-02
影响因子：
4
通讯作者：
Hong JS
中科院分区：
文献类型：
--
作者：
Chen SH;Oyarzabal EA;Hong JS
随着世界各地平均预期寿命的延长，神经退行性疾病已成为现代全球最大的公共卫生挑战之一。过去几十年来，人们在研究神经退行性疾病方面做出了巨大努力，但其散发性的特点使得揭示其病因具有挑战性。越来越多的证据表明，应激和垂死神经元释放的损伤相关分子模式（DAMP）等因素可能与疾病病理学有关，并刺激小胶质细胞的慢性激活，从而导致神经元氧化应激和变性。本综述重点关注小胶质细胞整合素受体 Mac1 及其下游效应子 NADPH 氧化酶 (NOX2) 如何有助于维持慢性神经炎症，并对神经退行性疾病中炎症驱动的神经毒性至关重要。我们的希望是提供关于可以减缓甚至阻止神经退行性变的新靶点和疗法的新见解。
As average life expectancy rises throughout the world, neurodegenerative diseases have emerged as one of the greatest global public heath challenges in modern times. Substantial efforts have been made in researching neurodegenerative diseases over the last few decades, yet their predominantly sporadic nature has made uncovering their etiologies challenging. Mounting evidence has suggested that factors like damage-associated molecular patterns (DAMPs) released by stressed and dying neurons are likely involved in disease pathology and in stimulating chronic activation of microglia that contributes to neuronal oxidative stress and degeneration. This review focuses on how the microglial integrin receptor Mac1 and its downstream effector NADPH oxidase (NOX2) contribute to maintaining chronic neuroinflammation and are crucial in inflammation-driven neurotoxicity in neurodegenerative diseases. Our hope is to provide new insights on novel targets and therapies that could slow or even halt neurodegeneration.