Institute for Biomedical Technologies (ITB-CNR) , Segrate, Italy.
J Proteome Res. 2013 Dec 6;12(12):5642-55. doi: 10.1021/pr400583h. Epub 2013 Oct 21.
In systemic amyloidosis, accumulation of misfolded proteins as extracellular amyloid fibrils in tissues causes severe organ dysfunction, but the molecular events of tissue damage related to amyloid deposition are still largely unknown. Through the use of the MudPIT proteomic approach, comprehensive protein profiles of human amyloid-affected adipose tissue from patients and its control (non-amyloid-affected) counterpart were acquired. Label-free comparison between patients and controls made it possible to highlight differences related to the presence of amyloid, by describing up- and down-represented proteins, connected into interacting networks. In particular, extracellular matrix (ECM), protein folding, lipid metabolism, and mitochondrial functions were among the most affected structural/functional pathways. The reported results, obtained with no a priori hypotheses, represent a significant step forward in the clarification of the molecular mechanisms involved in amyloidoses at tissue level and are the premise for understanding protein misfolding diseases.
在系统性淀粉样变性中，错误折叠的蛋白质在组织中积累为细胞外的淀粉样纤维，导致严重的器官功能障碍，但与淀粉样沉积相关的组织损伤的分子事件在很大程度上仍不清楚。通过使用 MudPIT 蛋白质组学方法，获得了来自患者的受淀粉样蛋白影响的脂肪组织及其对照（不受淀粉样蛋白影响）的综合蛋白质图谱。患者与对照组之间的无标记比较使我们能够通过描述上调和下调的蛋白质并将其连接成相互作用的网络，突出与淀粉样蛋白存在相关的差异。特别是细胞外基质 (ECM)、蛋白质折叠、脂质代谢和线粒体功能是受影响最严重的结构/功能途径之一。这些没有先验假设的报告结果代表了在组织水平阐明淀粉样变性相关分子机制的重要一步，也是理解蛋白质错误折叠疾病的前提。
