Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications.
Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications.
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DOI：
10.3390/ijms22116016
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发表时间：
2021-06-02
影响因子：
5.6
通讯作者：
Misasi R
中科院分区：
文献类型：
--
作者：
Candelise N;Scaricamazza S;Salvatori I;Ferri A;Valle C;Manganelli V;Garofalo T;Sorice M;Misasi R
内在无序是多肽链的一种自然特征，导致缺乏明确的三维结构。蛋白质内在无序区域的构象变化导致不稳定的β-Sheet富集物，这些中间体通过与其他β-Sheet富集物分子间的相互作用而稳定，产生稳定的蛋白质聚集体。在错误折叠时，根据氨基酸链的组成和周围环境，可能会采取几种途径，导致不同的结构。越来越多的证据表明，蛋白质的构象状态可能启动了与病理学和生理学有关的信号通路。在这篇综述中，我们将总结由内在无序的蛋白质结构域产生的结构的异质性，并重点介绍导致生理液滴和致病聚集体形成的途径。将讨论在神经退行性疾病的聚集体中发现的最常见的蛋白质及其结构的变异性。我们将进一步评估蛋白质聚集体结构异质性研究的临床意义和未来应用，这可能有助于理解在神经退行性疾病中观察到的表型多样性。
Intrinsic disorder is a natural feature of polypeptide chains, resulting in the lack of a defined three-dimensional structure. Conformational changes in intrinsically disordered regions of a protein lead to unstable β-sheet enriched intermediates, which are stabilized by intermolecular interactions with other β-sheet enriched molecules, producing stable proteinaceous aggregates. Upon misfolding, several pathways may be undertaken depending on the composition of the amino acidic string and the surrounding environment, leading to different structures. Accumulating evidence is suggesting that the conformational state of a protein may initiate signalling pathways involved both in pathology and physiology. In this review, we will summarize the heterogeneity of structures that are produced from intrinsically disordered protein domains and highlight the routes that lead to the formation of physiological liquid droplets as well as pathogenic aggregates. The most common proteins found in aggregates in neurodegenerative diseases and their structural variability will be addressed. We will further evaluate the clinical relevance and future applications of the study of the structural heterogeneity of protein aggregates, which may aid the understanding of the phenotypic diversity observed in neurodegenerative disorders.
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DOI：
10.1016/j.bbapap.2010.04.001
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Biancalana M;Koide S
通讯作者：
Koide S
影响因子：
16.6
作者：
Ambadipudi S;Biernat J;Riedel D;Mandelkow E;Zweckstetter M
通讯作者：
Zweckstetter M
影响因子：
4.8
作者：
Babinchak, W. Michael;Haider, Raza;Surewicz, Witold K.
通讯作者：
Surewicz, Witold K.
影响因子：
9
作者：
Area-Gomez E;de Groof A;Bonilla E;Montesinos J;Tanji K;Boldogh I;Pon L;Schon EA
通讯作者：
Schon EA
影响因子：
19
作者：
Boeynaems S;Alberti S;Fawzi NL;Mittag T;Polymenidou M;Rousseau F;Schymkowitz J;Shorter J;Wolozin B;Van Den Bosch L;Tompa P;Fuxreiter M
通讯作者：
Fuxreiter M