Wilson Mark R, Yerbury Justin J, Poon Stephen
School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia.
Mol Biosyst. 2008 Jan;4(1):42-52. doi: 10.1039/b712728f. Epub 2007 Nov 19.
The in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors may be critical parts of a quality control system to protect the body against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerbate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.
称为淀粉样蛋白的纤维状蛋白质沉积物在体内的形成与40多种严重人类疾病相关，这些疾病统称为蛋白质沉积病。在许多情况下，淀粉样蛋白沉积物位于细胞外，并且发现与新鉴定出的丰富细胞外伴侣蛋白（ECs）有关。有证据表明ECs在体内淀粉样蛋白的形成和清除中起重要调节作用。提出了一个模型，该模型认为，在正常情况下，ECs通过与细胞外错误折叠的蛋白质结合来使其稳定，然后将它们引导至特定的细胞受体进行摄取和随后的降解。因此，ECs及其受体可能是保护身体免受危险疏水蛋白质/肽侵害的质量控制系统的关键部分。然而，在疾病期间可能出现的错误折叠蛋白摩尔过量的情况下，有限数量的可用ECs实际上可能会加剧病理状况，这似乎也是有可能的。在理解控制细胞外蛋白质折叠机制方面的进一步进展可能会确定有效的疾病治疗新策略。
