5′-Adenosine Monophosphate-Activated Protein Kinase-Mammalian Target of Rapamycin Axis As Therapeutic Target for Age-Related Macular Degeneration
5′-Adenosine Monophosphate-Activated Protein Kinase-Mammalian Target of Rapamycin Axis As Therapeutic Target for Age-Related Macular Degeneration
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DOI：
10.1089/rej.2011.1220
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发表时间：
2011-12-01
影响因子：
2.6
通讯作者：
Kaarniranta, Kai
中科院分区：
文献类型：
--
作者：
Hyttinen, Juha M. T.;Petrovski, Goran;Kaarniranta, Kai
在发达国家，老年性黄斑变性（AMD）是最常见的致盲原因。AMD本质上涉及慢性氧化应激、视网膜色素上皮（RPE）细胞中脂褐素积累增加、细胞外囊肿形成以及视网膜慢性炎症的存在。衰老细胞阻止细胞毒性蛋白聚集体积累的能力下降，这可能引起有丝分裂后RPE细胞中脂褐素积累到溶酶体中。脂褐素的形成，反过来，降低溶酶体酶活性和损害自噬清除受损蛋白的目的是细胞清除。5'-腺苷单磷酸活化蛋白激酶（AMPK）是一种众所周知的哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，随后诱导自噬。本文综述了AMPK-mTOR轴上新的潜在治疗靶点，以及自噬清除抑制或预防RPE变性和AMD发展的途径。
Age-related macular degeneration (AMD) is the most common reason for blindness in developed countries. AMD essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells, and extracellular drusen formation, as well as presence of chronic inflammation in the retina. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells, which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. The formation of lipofuscin, in turn, decreases the lysosomal enzyme activity and impairs the autophagic clearance of damaged proteins destined for cellular removal. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a well-known inhibitor of mammalian target of rapamycin (mTOR) that subsequently evokes induction of autophagy. This review examines the novel potential therapeutic targets on the AMPK-mTOR axis and the ways in which autophagy clearance can suppress or prevent RPE degeneration and development of AMD.