Wang Steven S-S, Wu Josephine W, Yamamoto Shuichi, Liu Hwai-Shen
Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
Biotechnol J. 2008 Feb;3(2):165-92. doi: 10.1002/biot.200700065.
Protein aggregation is a ubiquitous phenomenon significant to all aspects of science. Notably, the formation of protein aggregates is frequently encountered in biochemical research and biopharmaceutical industry. Formation of protein aggregates is generally regarded to be associated with partially folded intermediate species that are susceptible to self-association due to the exposure of hydrophobic core. Evidence supports the concept that the formation of aggregates in vitro is a generic property of proteins. In human etiology, more than 20 different devastating human diseases have been reported to be associated with protein aggregation. Although protein aggregation diseases have been the center of intense research, much remains to be learned regarding the underlying molecular mechanisms. In this review, the general background information on protein aggregation is first provided. Next, we summarize the properties, characteristics and causes of protein aggregates. Finally, from the perspectives of epidemiology, pathogenesis, existing mechanisms, relevant hypotheses, and current as well as potential therapeutic approaches, two examples of protein aggregation diseases, Alzheimer's disease and cataract, are briefly discussed. Importantly, while a variety of molecules have been suggested, the effective therapeutic drugs for curing the diseases involving protein aggregation have yet to be identified. We believe that a better understanding of the mechanisms of protein aggregation process and an extensive investigation into the drug penetration, efficacy, and side effects will certainly aid in developing the successful pharmacological agents for these diseases.
蛋白质聚集是一种普遍存在的现象，对科学的各个方面都具有重要意义。值得注意的是，在生化研究和生物制药行业中经常会遇到蛋白质聚集体的形成。蛋白质聚集体的形成通常被认为与部分折叠的中间物种有关，这些中间物种由于疏水核心的暴露而易于自我缔合。有证据支持这样的观点，即体外聚集体的形成是蛋白质的一种普遍特性。在人类病因学中，据报道有20多种不同的毁灭性人类疾病与蛋白质聚集有关。尽管蛋白质聚集疾病一直是深入研究的核心，但关于其潜在的分子机制仍有许多有待了解。在这篇综述中，首先提供了关于蛋白质聚集的一般背景信息。接下来，我们总结了蛋白质聚集体的性质、特征和成因。最后，从流行病学、发病机制、现有机制、相关假说以及当前和潜在的治疗方法等角度，简要讨论了两种蛋白质聚集疾病的例子，即阿尔茨海默病和白内障。重要的是，虽然已经提出了多种分子，但尚未确定治疗涉及蛋白质聚集疾病的有效治疗药物。我们相信，更好地理解蛋白质聚集过程的机制，并广泛研究药物的渗透性、疗效和副作用，肯定有助于开发出针对这些疾病的成功药物。
