Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.
Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.
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DOI：
10.1186/s13024-022-00528-w
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发表时间：
2022-03-28
影响因子：
15.1
通讯作者：
Zhang SX
中科院分区：
文献类型：
--
作者：
McLaughlin T;Medina A;Perkins J;Yera M;Wang JJ;Zhang SX
视网膜作为中枢神经系统（CNS）的一部分，在哺乳动物中具有有限的自我修复和再生能力，由于高能量需求和快速的蛋白质周转而处于累积的环境压力下。这些应激源破坏细胞蛋白质和代谢稳态，如果不减轻，可导致视网膜神经元的功能障碍和细胞死亡。一种主要的细胞应激反应是高度保守的未折叠蛋白反应（UPR）。UPR通过三种主要的信号传导途径起作用，试图通过各种手段恢复内质网（ER）中的蛋白质稳态，包括但不限于减少蛋白质翻译、增加蛋白质折叠能力和促进错误折叠的蛋白质降解。此外，最近的工作已经确定了UPR在调节细胞代谢和线粒体功能中的新功能，其干扰有助于神经元变性和功能障碍。在过去的二十年中，已经探索了UPR在老化期间以及在年龄相关性黄斑变性（AMD）、色素性视网膜炎（RP）、青光眼和糖尿病性视网膜病变（DR）的疾病条件下在视网膜神经元中的作用。每种疾病及其相应的动物模型都提供了独特的挑战和独特的机会，以更好地了解UPR在维持视网膜健康和功能中的作用。我们使用以下关键词在PubMed和Google Scholar上进行了广泛的文献检索：未折叠蛋白反应、代谢、ER应激、视网膜变性、衰老、年龄相关性黄斑变性、视网膜色素变性、青光眼、糖尿病视网膜病变。我们总结了最近的进展，了解细胞的应激反应，特别是UPR，在视网膜疾病，突出的潜在作用，UPR途径的调节细胞代谢和线粒体功能的视网膜神经元。此外，我们提供的前景和挑战，针对UPR途径作为一种新的治疗方法，在年龄和疾病相关的视网膜变性的前景和挑战。
The retina, as part of the central nervous system (CNS) with limited capacity for self-reparation and regeneration in mammals, is under cumulative environmental stress due to high-energy demands and rapid protein turnover. These stressors disrupt the cellular protein and metabolic homeostasis, which, if not alleviated, can lead to dysfunction and cell death of retinal neurons. One primary cellular stress response is the highly conserved unfolded protein response (UPR). The UPR acts through three main signaling pathways in an attempt to restore the protein homeostasis in the endoplasmic reticulum (ER) by various means, including but not limited to, reducing protein translation, increasing protein-folding capacity, and promoting misfolded protein degradation. Moreover, recent work has identified a novel function of the UPR in regulation of cellular metabolism and mitochondrial function, disturbance of which contributes to neuronal degeneration and dysfunction. The role of the UPR in retinal neurons during aging and under disease conditions in age-related macular degeneration (AMD), retinitis pigmentosa (RP), glaucoma, and diabetic retinopathy (DR) has been explored over the past two decades. Each of the disease conditions and their corresponding animal models provide distinct challenges and unique opportunities to gain a better understanding of the role of the UPR in the maintenance of retinal health and function. We performed an extensive literature search on PubMed and Google Scholar using the following keywords: unfolded protein response, metabolism, ER stress, retinal degeneration, aging, age-related macular degeneration, retinitis pigmentosa, glaucoma, diabetic retinopathy. We summarize recent advances in understanding cellular stress response, in particular the UPR, in retinal diseases, highlighting the potential roles of UPR pathways in regulation of cellular metabolism and mitochondrial function in retinal neurons. Further, we provide perspective on the promise and challenges for targeting the UPR pathways as a new therapeutic approach in age- and disease-related retinal degeneration.
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影响因子：
3.5
作者：
Agrawal SA;Burgoyne T;Eblimit A;Bellingham J;Parfitt DA;Lane A;Nichols R;Asomugha C;Hayes MJ;Munro PM;Xu M;Wang K;Futter CE;Li Y;Chen R;Cheetham ME
通讯作者：
Cheetham ME
影响因子：
5.3
作者：
Ansar M;Santos-Cortez RL;Saqib MA;Zulfiqar F;Lee K;Ashraf NM;Ullah E;Wang X;Sajid S;Khan FS;Amin-ud-Din M;University of Washington Center for Mendelian Genomics;Smith JD;Shendure J;Bamshad MJ;Nickerson DA;Hameed A;Riazuddin S;Ahmed ZM;Ahmad W;Leal SM
通讯作者：
Leal SM
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
影响因子：
7.4
作者：
Cano, Marisol;Wang, Lei;Wan, Jun;Barnett, Bradley P.;Ebrahimi, Katayoon;Qian, Jiang;Handa, James T.
通讯作者：
Handa, James T.
从疾病描述和基因发现到功能性细胞途径：TMCO1长达十年的旅程。
影响因子：
3.7
作者：
Batchelor-Regan H;Xin B;Zhou A;Wang H
通讯作者：
Wang H