摘要
丙氨酸的功能缺陷:乙醛酸氨基转移酶(AGT)在人类肝细胞导致一种罕见的隐性遗传疾病,称为原发性高草酸尿症I型(PH1)。原发性高草酸尿症I型的特点是在肾脏和泌尿道逐步积累和沉积草酸钙结石,导致危及生命的和潜在的致命条件。在过去的几十年中,疾病的分子发病机制的实质性进展的阐述已取得进展。导致了一些方面的理解,许多突变导致乙醛酸氨基转移酶缺乏通过影响导致降低表达水平的蛋白折叠途径,增加的聚集倾向,和/或异常的线粒体定位。因此,可以认为是一个错误折叠疾病原发性高草酸尿症I型,旨在抵消变异的构象缺陷可能治疗方法。在这篇综述中,我们总结了在发展的识别分子救援乙醛酸氨基转移酶折叠运输新策略进展,无论是作为药物分子伴侣或防止蛋白质靶向错误。
关键词: 原发性高草酸尿症I型,丙氨酸,乙醛酸氨基转移酶,错误折叠疾病,5’-磷酸吡哆醛,致病变种,药物分子伴侣。
图形摘要
Current Drug Targets
Title:Natural and Unnatural Compounds Rescue Folding Defects of Human Alanine: Glyoxylate Aminotransferase Leading to Primary Hyperoxaluria Type I
Volume: 17 Issue: 13
Author(s): Elisa Oppici, Riccardo Montioli, Mirco Dindo, Barbara Cellini
Affiliation:
关键词: 原发性高草酸尿症I型,丙氨酸,乙醛酸氨基转移酶,错误折叠疾病,5’-磷酸吡哆醛,致病变种,药物分子伴侣。
摘要: The functional deficit of alanine:glyoxylate aminotransferase (AGT) in human hepatocytes leads to a rare recessive disorder named primary hyperoxaluria type I (PH1). PH1 is characterized by the progressive accumulation and deposition of calcium oxalate stones in the kidneys and urinary tract, leading to a life-threatening and potentially fatal condition. In the last decades, substantial progress in the clarification of the molecular pathogenesis of the disease have been made. They resulted in the understanding that many mutations cause AGT deficiency by affecting the folding pathway of the protein leading to a reduced expression level, an increased aggregation propensity, and/or an aberrant mitochondrial localization. Thus, PH1 can be considered a misfolding disease and possibly treated by approaches aimed at counteracting the conformational defects of the variants. In this review, we summarize recent advances in the development of new strategies to identify molecules able to rescue AGT folding and trafficking either by acting as pharmacological chaperones or by preventing the mistargeting of the protein.
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Cite this article as:
Elisa Oppici, Riccardo Montioli, Mirco Dindo, Barbara Cellini , Natural and Unnatural Compounds Rescue Folding Defects of Human Alanine: Glyoxylate Aminotransferase Leading to Primary Hyperoxaluria Type I, Current Drug Targets 2016; 17 (13) . https://dx.doi.org/10.2174/1389450117666160302095254
DOI https://dx.doi.org/10.2174/1389450117666160302095254 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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