Amyloid Disassembly: What Can We Learn from Chaperones?
Amyloid Disassembly: What Can We Learn from Chaperones?
复制标题
DOI：
10.3390/biomedicines10123276
复制
发表时间：
2022-12-17
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
蛋白质聚集和随后聚集的具有交叉β结构的不溶性淀粉样纤维是淀粉样病的内在特征，即淀粉样变性。淀粉样蛋白的形成涉及一系列途径上和途径外的蛋白质聚集事件，导致成熟的不溶性纤维最终在多种组织中积累。在这一系列事件中，形成了可溶性低聚物，它们是淀粉样蛋白级联过程中最具细胞毒性的分子实体之一。这些淀粉样蛋白可溶低聚物和淀粉样蛋白原纤维和纤维在一些组织和器官中直接或间接作用，在某些情况下导致细胞死亡，一般情况下导致器官功能障碍。有几十种不同的蛋白质和多肽导致多种淀粉样变性疾病，其中最主要的是阿尔茨海默氏症、帕金森氏症、亨廷顿氏症和其他几种神经退行性疾病。淀粉样原纤维分解是目前正在寻求的克服淀粉样蛋白病理的疾病修改治疗策略之一。清除预先形成的淀粉样蛋白，从而阻止器官恶化的进程，可能会提高患者的存活率和生活质量。在这篇综述中，我们从文献中收集了许多能够分解预制淀粉样蛋白的化学和生化制剂的例子，它们被分类为分子伴侣、化学伴侣和药理伴侣。我们重点介绍了它们的作用方式、化学结构、与纤维结构的相互作用、解聚产物的形态和毒性，以及解聚剂作为淀粉样变性治疗选择的潜在用途。
Protein aggregation and subsequent accumulation of insoluble amyloid fibrils with cross-β structure is an intrinsic characteristic of amyloid diseases, i.e., amyloidoses. Amyloid formation involves a series of on-pathway and off-pathway protein aggregation events, leading to mature insoluble fibrils that eventually accumulate in multiple tissues. In this cascade of events, soluble oligomeric species are formed, which are among the most cytotoxic molecular entities along the amyloid cascade. The direct or indirect action of these amyloid soluble oligomers and amyloid protofibrils and fibrils in several tissues and organs lead to cell death in some cases and organ disfunction in general. There are dozens of different proteins and peptides causing multiple amyloid pathologies, chief among them Alzheimer’s, Parkinson’s, Huntington’s, and several other neurodegenerative diseases. Amyloid fibril disassembly is among the disease-modifying therapeutic strategies being pursued to overcome amyloid pathologies. The clearance of preformed amyloids and consequently the arresting of the progression of organ deterioration may increase patient survival and quality of life. In this review, we compiled from the literature many examples of chemical and biochemical agents able to disaggregate preformed amyloids, which have been classified as molecular chaperones, chemical chaperones, and pharmacological chaperones. We focused on their mode of action, chemical structure, interactions with the fibrillar structures, morphology and toxicity of the disaggregation products, and the potential use of disaggregation agents as a treatment option in amyloidosis.
登录
查看更多内容
影响因子：
120.7
作者：
Berk, John L.;Suhr, Ole B.;Obici, Laura;Sekijima, Yoshiki;Zeldenrust, Steven R.;Yamashita, Taro;Heneghan, Michael A.;Gorevic, Peter D.;Litchy, William J.;Wiesman, Janice F.;Nordh, Erik;Corato, Manuel;Lozza, Alessandro;Cortese, Andrea;Robinson-Papp, Jessica;Colton, Theodore;Rybin, Denis V.;Bisbee, Alice B.;Ando, Yukio;Ikeda, Shu-ichi;Seldin, David C.;Merlini, Giampaolo;Skinner, Martha;Kelly, Jeffery W.;Dyck, Peter J.
通讯作者：
Dyck, Peter J.
影响因子：
8
作者：
Arora, A;Ha, C;Park, CB
通讯作者：
Park, CB
影响因子：
6.1
作者：
Abioye, Raliat O.;Okagu, Ogadimma D.;Udenigwe, Chibuike C.
通讯作者：
Udenigwe, Chibuike C.
影响因子：
7.4
作者：
Cardoso I;Martins D;Ribeiro T;Merlini G;Saraiva MJ
通讯作者：
Saraiva MJ
影响因子：
--
作者：
Bae J;Kim N;Shin Y;Kim SY;Kim YJ
通讯作者：
Kim YJ