Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration.
Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration.
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DOI：
10.1007/978-1-4419-1399-9_46
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发表时间：
2010
影响因子：
--
通讯作者：
Gould, Douglas B.
中科院分区：
文献类型：
--
作者：
Libby, Richard T.;Gould, Douglas B.
年龄相关性黄斑变性（AMD）是一种多因素疾病，也是导致失明的主要原因。蛋白质组学和遗传数据表明，先天免疫的替代补体级联的激活或去抑制与终末期疾病有关。多项证据表明，活性氧的产生和慢性氧化应激会导致蛋白质和脂质发生修饰，从而启动补体级联反应。了解这些致病途径的触发因素和主要损伤的部位对于靶向治疗的开发非常重要。来自错误折叠突变蛋白和其他来源的内质网（ER）应激是一个重要的潜在支流机制。我们提出，视网膜色素上皮和/或脉络膜中错误折叠蛋白诱导的内质网应激可能导致慢性氧化应激、补体失调和AMD。针对内质网应激和氧化应激的小分子可以实现从疾病治疗到疾病预防的转变。
Age-related macular degeneration (AMD) is a multi-factorial disease and a leading cause of blindness. Proteomic and genetic data suggest that activation or de-repression of the alternate complement cascade of innate immunity is involved in end-stage disease. Several lines of evidence suggest that production of reactive oxygen species and chronic oxidative stress lead to protein and lipid modifications that initiate the complement cascade. Understanding the triggers of these pathogenic pathways and the site of the primary insult will be important for development of targeted therapeutics. Endoplasmic reticulum (ER) stress from misfolded mutant proteins and other sources are an important potential tributary mechanism. We propose that misfolded-protein-induced ER stress in the retinal-pigmented epithelium and/or choroid could lead to chronic oxidative stress, complement deregulation and AMD. Small molecules targeted to ER stress and oxidative stress could allow for a shift from disease treatment to disease prevention.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
--
作者：
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通讯作者：
Chew, EY
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
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通讯作者：
Hollyfield, JG
影响因子：
5.6
作者：
Dong, Aling;Xie, Bing;Shen, Jikui;Yoshida, Tsunehiko;Yokoi, Katsutoshi;Hackett, Sean F.;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
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