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醛脱氢酶1家族:一种潜在的疾病分子靶点。

Aldehyde dehydrogenase 1 family: A potential molecule target for diseases.

作者信息

Duan Xiangning, Hu Haoliang, Wang Lingzhi, Chen Linxi

机构信息

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China.

Changde Research Centre for Artificial Intelligence and Biomedicine, Zoology Key Laboratory of Hunan Higher Education, College of Life and Environmental Sciences, Hunan University of Arts and Science, Changde, Hunan, China.

出版信息

Cell Biol Int. 2024 May 27. doi: 10.1002/cbin.12188.

Abstract

Aldehyde dehydrogenase 1 (ALDH1), a crucial aldehyde metabolizing enzyme, has six family members. The ALDH1 family is expressed in various tissues, with a significant presence in the liver. It plays a momentous role in several pathophysiological processes, including aldehyde detoxification, oxidative stress, and lipid peroxidation. Acetaldehyde detoxification is the fundamental function of the ALDH1 family in participating in vital pathological mechanisms. The ALDH1 family can catalyze retinal to retinoic acid (RA) that is a hormone-signaling molecule and plays a vital role in the development and adult tissues. Furthermore, there is a need for further and broader research on the role of the ALDH1 family as a signaling molecule. The ALDH1 family is widely recognized as a cancer stem cell (CSC) marker and plays a significant role in the proliferation, invasion, metastasis, prognosis, and drug resistance of cancer. The ALDH1 family also participates in other human diseases, such as neurodegenerative diseases, osteoarthritis, diabetes, and atherosclerosis. It can inhibit disease progression by inhibiting/promoting the expression/activity of the ALDH1 family. In this review, we comprehensively analyze the tissue distribution, and functions of the ALDH1 family. Additionally, we review the involvement of the ALDH1 family in diseases, focusing on the underlying pathological mechanisms and briefly talk about the current status and development of ALDH1 family inhibitors. The ALDH1 family presents new possibilities for treating diseases, with both its upstream and downstream pathways serving as promising targets for therapeutic intervention. This offers fresh perspectives for drug development in the field of disease research.

摘要

醛脱氢酶1(ALDH1)是一种关键的醛代谢酶,有六个家族成员。ALDH1家族在多种组织中表达,在肝脏中含量丰富。它在几个病理生理过程中发挥着重要作用,包括醛解毒、氧化应激和脂质过氧化。乙醛解毒是ALDH1家族参与重要病理机制的基本功能。ALDH1家族可以催化视黄醛转化为视黄酸(RA),视黄酸是一种激素信号分子,在发育和成年组织中发挥重要作用。此外,需要对ALDH1家族作为信号分子的作用进行更深入、更广泛的研究。ALDH1家族被广泛认为是一种癌症干细胞(CSC)标志物,在癌症的增殖、侵袭、转移、预后和耐药性方面发挥着重要作用。ALDH1家族还参与其他人类疾病,如神经退行性疾病、骨关节炎、糖尿病和动脉粥样硬化。可以通过抑制/促进ALDH1家族的表达/活性来抑制疾病进展。在这篇综述中,我们全面分析了ALDH1家族的组织分布和功能。此外,我们综述了ALDH1家族在疾病中的参与情况,重点关注潜在的病理机制,并简要介绍了ALDH1家族抑制剂的现状和发展。ALDH1家族为疾病治疗提供了新的可能性,其上游和下游途径都是有前景的治疗干预靶点。这为疾病研究领域的药物开发提供了新的视角。

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