摘要
有些天然蛋白质可通过错误折叠形成淀粉样纤维,并进一步沉积导致淀粉样病变,被认为是许多重大人类疾病的病理基础。因此,阐明天然蛋白质错误折叠、聚集形成淀粉样纤维的分子机制,是预防、诊断和治疗相关疾病的关键。研究者们从天然蛋白质中鉴定出许多能够形成淀粉样纤维的关键短肽片段,即淀粉样短肽,对它们形成淀粉样纤维的能力及其在完整蛋白质聚集过程中的决定性作用进行深入研究。本文对近年来人类疾病相关淀粉样短肽的研究展开综述。首先,介绍鉴定淀粉样短肽的标准及其相应的研究方法和技术手段;并回顾近年来与一些重大人类疾病相关的淀粉样短肽,尤其是与神经退行性疾病相关淀粉样短肽的进展情况,对淀粉样短肽中出现频率较高的氨基酸残基及其可能的自组装原理进行总结分析;最后,展望这些淀粉样短肽作为靶点在相关疾病诊断和治疗方面的意义,并初步探讨它们作为新型生物材料在生物医学工程领域的应用前景。本文一方面为阐明天然蛋白质形成淀粉样沉淀的分子机制提供参考,另一方面也为相关疾病的治疗提供思路,同时也为新型生物材料的开发提出潜在的可能性。
Some natural proteins could misfold into amyloid fibrils and further deposit to cause amyloidosis,which has been believed to be the pathogenic basis of many important human diseases.Illustrating the molecular mechanism of how natural proteins misfold and aggregate into amyloid fibrils holds the key to prevent,diagnose and cure related diseases.For this purpose,many amyloid peptides,e.g.critical peptide fragments that can form amyloid fibrils on their own have been identified from natural proteins.Their ability to form amyloid fibrils,as well as their determinative role in the aggregation of fulllength proteins,have been extensively studied.In this paper we reviewed recent research progress on different amyloid peptides associated with human diseases.Firstly we introduced the criteria to identify amyloid peptides and corresponding investigating methods and techniques.Then we reviewed recent progress on some amyloid peptides associated with major human diseases,especially some neurodegenerative diseases.Amino acid residues frequently appeared in these amyloid peptides were summarized,and their possible self-assembling mechanisms were analyzed.Finally,we prospected the important implication of these amyloid peptides as potential targets for the diagnosis and treatment of related diseases,and discussed their possible applications in the field of biomedical engineering as novel biomaterials.On one hand,this review might provide useful references for clarifying the molecular mechanism for the formation of amyloid fibrils by natural proteins.On the other hand,it also proposed a rational clue for the treatment of related diseases.Furthermore,it also introduced the possibility of exploring novel biomaterials based on amyloid peptides.
作者
李诗杰
陈咏竹
LI Shi-Jie;CHEN Yong-Zhu(National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University;Periodical Press of West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第4期357-363,共7页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家老年疾病临床医学研究中心(四川大学华西医院)项目(No.Z2018B21)
国家自然科学基金(No.31100565)资助。
关键词
淀粉样纤维
淀粉样短肽
神经退行性疾病
短肽自组装
amyloid fibrils
amyloid peptides
neurodegenerative diseases
peptide self-assembly
