自然和非自然的化合物修复人丙氨酸：乙醛酸氨基转移酶的折叠缺陷导致原发性高草酸尿症I型

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.

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