AIBP: A New Safeguard against Glaucomatous Neuroinflammation.
AIBP: A New Safeguard against Glaucomatous Neuroinflammation.
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AIBP：一种新的青光眼神经炎症保护措施。
作者：
青光眼是一组导致不可逆性失明的眼部疾病。它的特点是视神经轴突和视网膜神经节细胞(RGC)的多因素变性，导致视力丧失。青光眼发病机制的主要组成部分包括胶质细胞驱动的神经炎症和线粒体动力学和生物能量学的损害，导致视网膜神经变性。在这篇综述文章中，我们综述了载脂蛋白A-I结合蛋白(AIBP)作为一种重要的抗炎和神经保护因子在视网膜中的作用的最新证据。由于其与Toll样受体4(TLR4)的结合，细胞外AIBP选择性地从炎症和激活细胞的质膜上清除多余的胆固醇。这导致TLR4相关的、富含胆固醇的脂筏表达减少，并抑制下游炎症信号。细胞内AIBP定位于线粒体，并通过丝裂原蛋白1和2的泛素化来调节有丝分裂。重要的是，在小鼠模型和人类青光眼视网膜中，高眼压导致AIBP缺乏。AIBP缺乏导致Müler神经胶质细胞TLR4的激活，引发视网膜神经节细胞和Müler神经胶质细胞的线粒体功能障碍，并影响小鼠的视觉功能。相反，恢复视网膜中AIBP的表达可以减少神经炎症，防止RGC死亡，并保护视觉功能。这些结果为AIBP在视网膜中的作用机制提供了新的见解，并提示在青光眼治疗中恢复视网膜AIBP表达的治疗潜力。
Glaucoma is a group of ocular diseases that cause irreversible blindness. It is characterized by multifactorial degeneration of the optic nerve axons and retinal ganglion cells (RGCs), resulting in the loss of vision. Major components of glaucoma pathogenesis include glia-driven neuroinflammation and impairment of mitochondrial dynamics and bioenergetics, leading to retinal neurodegeneration. In this review article, we summarize current evidence for the emerging role of apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory and neuroprotective factor in the retina. Due to its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from the plasma membrane of inflammatory and activated cells. This results in the reduced expression of TLR4-associated, cholesterol-rich lipid rafts and the inhibition of downstream inflammatory signaling. Intracellular AIBP is localized to mitochondria and modulates mitophagy through the ubiquitination of mitofusins 1 and 2. Importantly, elevated intraocular pressure induces AIBP deficiency in mouse models and in human glaucomatous retina. AIBP deficiency leads to the activation of TLR4 in Müller glia, triggering mitochondrial dysfunction in both RGCs and Müller glia, and compromising visual function in a mouse model. Conversely, restoring AIBP expression in the retina reduces neuroinflammation, prevents RGCs death, and protects visual function. These results provide new insight into the mechanism of AIBP function in the retina and suggest a therapeutic potential for restoring retinal AIBP expression in the treatment of glaucoma.
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影响因子：
6.7
作者：
Chen, Rui-Xiang;Jiang, Wang-Jie;Li, Chang-Xian
通讯作者：
Li, Chang-Xian
影响因子：
3.7
作者：
Astafurov K;Elhawy E;Ren L;Dong CQ;Igboin C;Hyman L;Griffen A;Mittag T;Danias J
通讯作者：
Danias J
DOI：
10.1038/s41580-020-00313-x
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Covarrubias AJ;Perrone R;Grozio A;Verdin E
通讯作者：
Verdin E
DOI：
10.1006/bbrc.2002.6756
发表时间：
2002-04-12
影响因子：
3.1
作者：
Duncan, KG;Bailey, KR;Schwartz, DM
通讯作者：
Schwartz, DM
影响因子：
8
作者：
Choi, Soo-Ho;Wallace, Aaron M.;Miller, Yury I.
通讯作者：
Miller, Yury I.