Self-assembly of protein aggregates in ageing disorders: the lens and cataract model
Self-assembly of protein aggregates in ageing disorders: the lens and cataract model
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DOI：
10.1098/rstb.2012.0104
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发表时间：
2013-05-05
影响因子：
6.3
通讯作者：
Clark, John I.
中科院分区：
文献类型：
--
作者：
Clark, John I.
白内障、神经退行性疾病、黄斑变性和衰老的病理学通常以蛋白质的缓慢进行性去稳定化及其自组装成淀粉样原纤维和聚集体为特征。在正常的细胞分化过程中，蛋白质自组装是细胞骨架组织的一种动力学机制。随着对衰老疾病的日益重视，人们对蛋白质自组装的小分子调节剂重新产生了兴趣。据报道，合成肽、小分子伴侣、适体、ATP和泛硫乙胺调节涉及以人α B-晶状体蛋白为代表的小应激蛋白及其靶标的自组装机制。小分子正被考虑作为分子治疗剂直接应用，以防止体内老化细胞和组织中的淀粉样蛋白和蛋白质聚集障碍。目前正在利用传统和创新技术鉴定用于有效调节蛋白质自组装的特定相互作用肽位点。小分子应激蛋白与其体内靶标之间的功能相互作用的定量仍然是研究的首要任务。控制体内蛋白质-蛋白质相互作用的定量参数需要表征，以了解正常细胞和衰老疾病中自组装系统的基本生物学。
Cataract, neurodegenerative disease, macular degeneration and pathologies of ageing are often characterized by the slow progressive destabilization of proteins and their self-assembly to amyloid-like fibrils and aggregates. During normal cell differentiation, protein self-assembly is well established as a dynamic mechanism for cytoskeletal organization. With the increased emphasis on ageing disorders, there is renewed interest in small-molecule regulators of protein self-assembly. Synthetic peptides, mini-chaperones, aptamers, ATP and pantethine reportedly regulate self-assembly mechanisms involving small stress proteins, represented by human alpha B-crystallin, and their targets. Small molecules are being considered for direct application as molecular therapeutics to protect against amyloid and protein aggregation disorders in ageing cells and tissues in vivo. The identification of specific interactive peptide sites for effective regulation of protein self-assembly is underway using conventional and innovative technologies. The quantification of the functional interactions between small stress proteins and their targets in vivo remains a top research priority. The quantitative parameters controlling protein-protein interactions in vivo need characterization to understand the fundamental biology of self-assembling systems in normal cells and disorders of ageing.