Del Monte Federica, Agnetti Giulio
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Proteomics Clin Appl. 2014 Aug;8(7-8):534-42. doi: 10.1002/prca.201400037.
A new concept in the field of heart-failure (HF) research points to a role of misfolded proteins, forming preamyloid oligomers (PAOs), in cardiac toxicity. This is largely based on few studies reporting the presence of PAOs, similar to those observed in neurodegenerative diseases, in experimental and human HF. As the majority of proteinopathies are sporadic in nature, protein post-translational modifications (PTMs) likely play a major role in this growing class of diseases. In fact, PTMs are known regulators of protein folding and of the formation of amyloid species in well-established proteinopathies. Proteomics has been instrumental in identifying both chemical and enzymatic PTMs, with a potential impact on protein mis-/folding. Here we provide the basics on how proteins fold along with a few examples of PTMs known to modulate protein misfolding and aggregation, with particular focus on the heart. Due to its innovative content and the growing awareness of the toxicity of misfolded proteins, an "Alzheimer's theory of HF" is timely. Moreover, the continuous innovations in proteomic technologies will help pinpoint PTMs that could contribute to the process. This nuptial between biology and technology could greatly assist in identifying biomarkers with increased specificity as well as more effective therapies.
心力衰竭（HF）研究领域的一个新概念指出，错误折叠的蛋白质形成淀粉样前体寡聚体（PAO）在心脏毒性中起作用。这主要基于少数研究报告，即在实验性和人类HF中存在PAO，类似于在神经退行性疾病中观察到的情况。由于大多数蛋白质病本质上是散发性的，蛋白质翻译后修饰（PTM）可能在这类不断增加的疾病中起主要作用。事实上，在已明确的蛋白质病中，PTM是蛋白质折叠和淀粉样物质形成的已知调节因子。蛋白质组学有助于识别化学和酶促PTM，这可能会对蛋白质错误折叠/折叠产生影响。在这里，我们提供了蛋白质如何折叠的基础知识，以及一些已知可调节蛋白质错误折叠和聚集的PTM示例，特别关注心脏。由于其创新内容以及对错误折叠蛋白质毒性的认识不断提高，“HF的阿尔茨海默病理论”应运而生。此外，蛋白质组学技术的不断创新将有助于确定可能促成这一过程的PTM。生物学与技术的这种结合可以极大地帮助识别具有更高特异性的生物标志物以及更有效的治疗方法。
