The superfamily of human aldehyde dehydrogenases (hALDHs) consists of 19 isoenzymes which are critical for several physiological and biosynthetic processes and play a major role in the organism’s detoxification via the NAD(P) dependent oxidation of numerous endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids. Over the last decades, ALDHs have been the subject of several studies as it was revealed that their differential expression patterns in various cancer types are associated either with carcinogenesis or promotion of cell survival. Here, we attempt to provide a thorough review of hALDHs’ diverse functions and 3D structures with particular emphasis on their role in cancer pathology and resistance to chemotherapy. We are especially interested in findings regarding the association of structural features and their changes with effects on enzymes’ functionalities. Moreover, we provide an updated outline of the hALDHs inhibitors utilized in experimental or clinical settings for cancer therapy. Overall, this review aims to provide a better understanding of the impact of ALDHs in cancer pathology and therapy from a structural perspective.
人类醛脱氢酶超家族包含19种同工酶，这些酶在多种生理和生物合成过程中至关重要，并通过依赖NAD(P)⁺的氧化反应将大量内源性和外源性醛类底物转化为相应羧酸，在机体解毒过程中发挥重要作用。近几十年来，醛脱氢酶已成为多项研究的焦点，因其在不同癌症类型中的差异表达模式与致癌过程或细胞存活促进密切相关。本文旨在系统综述人类醛脱氢酶的多样化功能与三维结构特征，重点探讨其在癌症病理学及化疗耐药中的作用机制。我们特别关注结构特征及其变化与酶功能调控关联性的最新发现，同时全面梳理当前实验研究与临床应用中用于癌症治疗的醛脱氢酶抑制剂研究进展。本综述旨在从结构生物学视角深化对醛脱氢酶在癌症病理机制与治疗中作用的理解。
肿瘤(癌症)患者之家