Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection.
Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection.
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DOI：
10.3390/cells12111539
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发表时间：
2023-06-03
期刊：
影响因子：
6
通讯作者：
Ju, Won-Kyu
中科院分区：
文献类型：
--
作者：
Bastola, Tonking;Perkins, Guy A.;Kim, Keun-Young;Choi, Seunghwan;Kwon, Jin-Woo;Shen, Ziyao;Strack, Stefan;Ju, Won-Kyu
关键词：
A-激酶锚定蛋白1(AKAP1)是一种多功能的线粒体支架蛋白，通过将包括蛋白激酶A在内的多种蛋白质锚定在线粒体外膜上，调节线粒体的动力学、生物能量学和钙稳态。青光眼是一种复杂的多因素疾病，其特征是视神经和视网膜神经节细胞(RGC)缓慢和进行性退化，最终导致视力丧失。线粒体网络和功能受损与青光眼神经变性有关。AKAP1的缺失诱导了动力蛋白相关蛋白1去磷酸化介导的线粒体断裂和视网膜节细胞的丢失。眼压升高导致青光眼视网膜AKAP1蛋白表达显著降低。AKAP1表达的扩增可保护视网膜节细胞免受氧化应激。因此，AKAP1的调节可以被认为是青光眼和其他线粒体相关视神经疾病神经保护干预的潜在治疗靶点。本文综述了AKAP1在维持视网膜节细胞线粒体动力学、生物能量学和有丝分裂中的作用，为寻找和开发新的治疗策略以保护视网膜节细胞及其轴突提供了科学依据。
A-Kinase anchoring protein 1 (AKAP1) is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis by anchoring several proteins, including protein kinase A, to the outer mitochondrial membrane. Glaucoma is a complex, multifactorial disease characterized by a slow and progressive degeneration of the optic nerve and retinal ganglion cells (RGCs), ultimately resulting in vision loss. Impairment of the mitochondrial network and function is linked to glaucomatous neurodegeneration. Loss of AKAP1 induces dynamin-related protein 1 dephosphorylation-mediated mitochondrial fragmentation and loss of RGCs. Elevated intraocular pressure triggers a significant reduction in AKAP1 protein expression in the glaucomatous retina. Amplification of AKAP1 expression protects RGCs from oxidative stress. Hence, modulation of AKAP1 could be considered a potential therapeutic target for neuroprotective intervention in glaucoma and other mitochondria-associated optic neuropathies. This review covers the current research on the role of AKAP1 in the maintenance of mitochondrial dynamics, bioenergetics, and mitophagy in RGCs and provides a scientific basis to identify and develop new therapeutic strategies that could protect RGCs and their axons in glaucoma.
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