Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms.
Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms.
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DOI：
10.3389/fmolb.2022.830006
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发表时间：
2022
影响因子：
5
通讯作者：
Bellotti V
中科院分区：
文献类型：
--
作者：
Faravelli G;Mondani V;Mangione PP;Raimondi S;Marchese L;Lavatelli F;Stoppini M;Corazza A;Canetti D;Verona G;Obici L;Taylor GW;Gillmore JD;Giorgetti S;Bellotti V
蛋白质球状到纤维状的转变是淀粉样蛋白疾病发展过程中的一个关键致病事件。尽管系统性淀粉样变性具有细胞外基质中淀粉样蛋白沉积的共同特征，但它们在临床上是不同的，因为受影响的器官可能不同。由于观察到淀粉样蛋白前体来源于循环中的球状血浆蛋白，人们试图阐明决定蛋白质从球状状态向纤维状态转变的结构事件。虽然变形的过程启发了从奥维德到卡夫卡的诗人和作家，但蛋白质变质是一个更新的概念。在生物化学中，它是研究蛋白质折叠范式和研究折叠动力学决定因素的理想隐喻。虽然我们已经学会了如何在体外将正常和致病的球状蛋白转化为纤维状聚合物，但在体内发生的事件要复杂得多，还没有得到解释。体内和体外的纤维形成模型之间仍然存在着很大的差距，因为这种疾病在活体中的生物学复杂性不能在试管中同等程度地复制。回顾在从细胞培养到人体组织等日益复杂的系统中监测球状蛋白淀粉样变性的主要科学尝试，可能有助于弥合实验模型和患者实际病理事件之间的差距。
The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients.
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影响因子：
5.6
作者：
Good SC;Dewison KM;Radford SE;van Oosten-Hawle P
通讯作者：
van Oosten-Hawle P
影响因子：
4
作者：
Dishman AF;Volkman BF
通讯作者：
Volkman BF
DOI：
10.1046/j.1432-1327.1998.2580061.x
发表时间：
1998-11-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bellotti, V;Stoppini, M;Ferri, G
通讯作者：
Ferri, G
影响因子：
2.9
作者：
COLON, W;KELLY, JW
通讯作者：
KELLY, JW
DOI：
10.1073/pnas.75.9.4499
发表时间：
1978-01-01
影响因子：
11.1
作者：
COSTA, PP;FIGUEIRA, AS;BRAVO, FR
通讯作者：
BRAVO, FR