The effect of glycosaminoglycans (GAGs) on amyloid aggregation and toxicity.
The effect of glycosaminoglycans (GAGs) on amyloid aggregation and toxicity.
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DOI：
10.3390/molecules20022510
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发表时间：
2015-02-02
期刊：
影响因子：
--
通讯作者：
Sirangelo I
中科院分区：
文献类型：
--
作者：
Iannuzzi C;Irace G;Sirangelo I
淀粉样变性是一种蛋白质折叠障碍，其中正常可溶性蛋白质作为不溶性原纤维沉积在细胞外，损害组织结构和功能。带电荷的聚电解质如糖胺聚糖（GAG）经常被发现与受淀粉样疾病影响的患者的组织中的蛋白质沉积相关。实验证据表明，它们可以在促进淀粉样纤维形成和稳定中发挥积极作用。GAG与淀粉样纤维的结合主要通过静电相互作用发生，涉及聚集蛋白的负电荷和带正电荷的侧链残基。与反应催化剂类似，GAG有利于聚集、成核和淀粉样蛋白原纤维形成，其作为结构模板用于将富含β-折叠的高细胞毒性寡聚前体自组装成无害的淀粉样蛋白原纤维。此外，通过淀粉样多肽和GAG分子之间的共有结合位点的特异性相互作用，可以促进GAG的淀粉样蛋白促进活性。本文综述了糖胺聚糖对淀粉样蛋白沉积以及与疾病无关的蛋白质的影响。此外，我们考虑了糖胺聚糖治疗淀粉样变性的潜力。
Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis.
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