Proteostasis in aging-associated ocular disease.
Proteostasis in aging-associated ocular disease.
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DOI：
10.1016/j.mam.2022.101157
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发表时间：
2022-12
影响因子：
10.6
通讯作者：
Taylor, Allen
中科院分区：
文献类型：
--
作者：
Weinberg, Jasper;Gaur, Mohita;Swaroop, Anand;Taylor, Allen
关键词：
视力障碍对人类生活质量具有毁灭性的后果。与视觉过程相关的细胞和组织必须在人的一生中发挥作用，并在暴露于各种损伤的情况下保持体内平衡。蛋白质组的维持称为蛋白质稳态，对于正常细胞功能至关重要，尤其是在高龄时。在这里，我们描述了蛋白质稳态的基本方面，从蛋白质合成和折叠到降解，并讨论了该领域的现状，特别关注与年龄相关的主要眼部疾病：年龄相关性黄斑变性、白内障和青光眼。我们的目的是让视觉科学家能够确定在何处以及如何利用蛋白质静态机制来扩展老化视网膜、晶状体和小梁网的功能稳态。尽管这些组织的新陈代谢截然不同，但还是出现了一些共同的主题。持续遭受侮辱，包括随着年龄增长的慢性压力，会增加蛋白质抑制负担，并降低降解机制的保真度，包括泛素蛋白酶体和识别并去除受损蛋白质的自噬溶酶体系统。这种“双重危险”导致细胞毒性蛋白随着年龄的增长呈指数积累。最后，我们讨论了维持蛋白质合成和降解途径适当平衡所面临的挑战，并建议利用蛋白质抑制能力应该为设计干预措施提供新的机会，以在与年龄相关的眼部疾病限制视力之前减轻这些疾病。
Vision impairment has devastating consequences for the quality of human life. The cells and tissues associated with the visual process must function throughout one’s life span and maintain homeostasis despite exposure to a variety of insults. Maintenance of the proteome is termed proteostasis, and is vital for normal cellular functions, especially at an advanced age. Here we describe basic aspects of proteostasis, from protein synthesis and folding to degradation, and discuss the current status of the field with a particular focus on major age-related eye diseases: age-related macular degeneration, cataract, and glaucoma. Our intent is to allow vision scientists to determine where and how to harness the proteostatic machinery for extending functional homeostasis in the aging retina, lens, and trabecular meshwork. Several common themes have emerged despite these tissues having vastly different metabolisms. Continued exposure to insults, including chronic stress with advancing age, increases proteostatic burden and reduces the fidelity of the degradation machineries including the ubiquitin-proteasome and the autophagy-lysosome systems that recognize and remove damaged proteins. This “double jeopardy” results in an exponential accumulation of cytotoxic proteins with advancing age. We conclude with a discussion of the challenges in maintaining an appropriate balance of protein synthesis and degradation pathways, and suggest that harnessing proteostatic capacities should provide new opportunities to design interventions for attenuating age-related eye diseases before they limit sight.
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