The BRICHOS domain was initially defined from sequence alignments of the Bri protein associated with familial dementia, chondromodulin associated with chondrosarcoma and surfactant protein C precursor (proSP‐C) associated with respiratory distress syndrome and interstitial lung disease (ILD). Today BRICHOS has been found in 12 protein families. Mutations in the Bri2 and proSP‐C genes result in familial dementia and ILD, respectively, and both these conditions are associated with amyloid formation. Amyloid is of great medical relevance as it is found in several major incurable diseases, like Alzheimer’s and Parkinson’s disease and diabetes mellitus. Work on recombinant BRICHOS domains and transfected cells indicate that BRICHOS is a chaperone domain that, during biosynthesis, binds to precursor protein regions with high β‐sheet propensities, thereby preventing them from amyloid formation. Regions prone to form β‐sheets are present in all BRICHOS‐containing precursor proteins and are probably eventually released by proteolytic cleavage, generating different peptides with largely unknown bioactivities. Recombinant BRICHOS domains from Bri2 and proSP‐C have been found to efficiently prevent SP‐C, the amyloid β‐peptide associated with Alzheimer’s disease, and medin, found in aortic amyloid, from forming amyloid fibrils. The data collected so far on BRICHOS raise several interesting topics for further research: (a) amyloid formation is a potential threat for many more proteins than the ones recognized so far in amyloid diseases; (b) amyloid formation of widely different peptides involves intermediate(s) that are recognized by the BRICHOS domain, suggesting that they have distinct structural similarities; and (c) the BRICHOS domain might be harnessed in therapeutic strategies against amyloid diseases.

中文翻译：

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与肺纤维化，痴呆和癌症相关的BRICHOS域–防止淀粉样蛋白原纤维形成的分子伴侣？

BRICHOS域最初是由与家族性痴呆相关的Bri蛋白，与软骨肉瘤相关的软骨调节蛋白和与呼吸窘迫综合征和间质性肺病（ILD）相关的表面活性剂蛋白C前体（proSP-C）的序列比对定义的。如今，已经在12个蛋白质家族中发现了BRICHOS。Bri2和proSP-C基因的突变分别导致家族性痴呆和ILD，这两种情况都与淀粉样蛋白形成有关。淀粉样蛋白具有重要的医学意义，因为它存在于几种主要的不可治愈的疾病中，例如阿尔茨海默氏病和帕金森氏病以及糖尿病。对重组BRICHOS结构域和转染细胞的研究表明，BRICHOS是一个分子伴侣结构域，在生物合成过程中，它与具有高β-折叠倾向的前体蛋白区域结合，从而防止它们形成淀粉样蛋白。在所有含BRICHOS的前体蛋白中都存在易于形成β-折叠的区域，这些区域最终可能会通过蛋白水解裂解而释放出来，从而产生具有很大程度上未知的生物活性的不同肽段。已发现Bri2和proSP‐C的重组BRICHOS结构域可有效防止SP‐C（与阿尔茨海默氏病相关的淀粉样β肽）和主动脉淀粉样中发现的medin形成淀粉样原纤维。迄今为止，在BRICHOS上收集的数据提出了一些有趣的话题，需要进一步研究：（a）淀粉样蛋白形成的潜在威胁比迄今为止在淀粉样蛋白疾病中公认的更多。（b）淀粉样蛋白形成的广泛不同的肽段涉及到BRICHOS域识别的中间体，表明它们具有明显的结构相似性；（c）BRICHOS结构域可用于对抗淀粉样变性疾病的治疗策略。