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人膜联蛋白A5:从生物标志物到药物候选物

Human Annexin A5:from Biomarkers to Therapeutic Candidates
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摘要 人膜联蛋白A5(human annexin A5,hAnxA5)是人体中一种重要的功能蛋白质分子,广泛存在于人体的细胞和体液中。hAnxA5作为具有特定结构、隶属于一个复杂成员膜联蛋白家族的一个成员分子,其生化特性也是非常独特的。它以钙离子依赖方式,可逆、特异性、高效地结合磷脂酰丝氨酸分子;并基于此特性发挥重要生物学功能,在诸多人体生理、病理现象中发挥重要作用。本文就hAnxA5的结构特点、生化特性、作用机制、影响效应以及在生物医学领域中的重要应用进行了较为系统的归纳与总结。游离态hAnxA5以单体形式存在,发挥生物学活性时通常形成聚合体形式。hAnxA5影响了人体的血管血栓疾病、自身免疫性疾病、肿瘤疾病、肺纤维化及肺损伤、非酒精性脂肪性肝炎等病理现象的发生与发展;hAnxA5作为疾病生物标志物,也应用在肿瘤、神经退行性疾病、心力衰竭、急性肾损伤和哮喘等疾病的研究中;作为新型药物候选物,hAnxA5及其衍生物被多次设计、运用于多类疾病的治疗探索,尤其在血管血栓类疾病的治疗探索上。对于hAnxA5的研究,仍存在某些空白与不足。对其研究的深入,不仅将拓展对于hAnxA5结构与功能关系的认识,而且将促进其在相关生物医学领域的应用。 Human annexin A5(hAnxA5)as an important functional protein molecule in the human body,widely exists in human cells and body fluids.hAnxA5,a member of annexin group with complex structure,exhibits a variety of biological functions by reversibly and specifically binding phosphatidylserine(PS)in a calcium-dependent manner and plays an important role in many human physiological processes.This paper has made induction and summary of the biochemical characteristics,mechanism,biological effects and important biomedical applications of hAnxA5.The hAnxA5 is present in the form of monomer and often exercise biological functions in a polymer.hAnxA5 affects the occurrence and development of pathological phenomena,such as vascular thrombosis disease,autoimmune disease,tumor disease,pulmonary fibrosis and lung injury,non-alcoholic fatty hepatitis,etc.As a biomarker,hAnxA5 has also been adopted in the study of diseases such as tumor,neurodegenerative diseases,heart failure,acute renal injury,asthma and so on.As novel drug candidates,hAnxA5 and its derivatives have been designed and applied to the therapeutic exploration of many kinds of diseases,especially for thrombotic diseases.There are also some gaps and shortcomings for hAnxA5 research.The in-depth of its research will not only expand the understanding of structure and functional relationships,but also promote its application in the field of biomedicine.
作者 张茜 孟庆玉 井健 ZHANG Xi;MENG Qing-Yu;JING Jian(College of Life Sciences,Beijing Key Laboratory of Biotechnology and Gene Engineering,Beijing Normal University,Bejing 100875,China)
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2022年第10期1311-1321,共11页 Chinese Journal of Biochemistry and Molecular Biology
基金 国家自然科学基金项目(No.30540071) 北京师范大学人才项目(No.104107977)资助。
关键词 人膜联蛋白A5 磷脂酰丝氨酸 生物标志物 靶向药物 凋亡检测 human annexin A5(hAnxA5) phosphatidylserine biomarker target drug apoptosis detection
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