The collagenopathies are a diverse group of diseases caused primarily by mutations in collagen genes. The resulting disruptions in collagen biogenesis can impair development, cause cellular dysfunction, and severely impact connective tissues. Most existing treatment options only address patient symptoms. Yet, while the disease-causing genes and proteins themselves are difficult to target, increasing evidence suggests that resculpting the intracellular proteostasis network, meaning the machineries responsible for producing and ensuring the integrity of collagen, could provide substantial benefit. We present a proteostasis-focused perspective on the collagenopathies, emphasizing progress toward understanding how mechanisms of collagen proteostasis are disrupted in disease. In parallel, we highlight recent advances in small molecule approaches to tune endoplasmic reticulum proteostasis that may prove useful in these disorders.

中文翻译：

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针对胶原蛋白病中的缺陷性蛋白稳态。

胶原病是主要由胶原基因突变引起的多种疾病。胶原生物发生的破坏会损害发育，引起细胞功能障碍并严重影响结缔组织。现有的大多数治疗方法只能解决患者的症状。然而，虽然致病基因和蛋白质本身很难靶向，但越来越多的证据表明，重新雕刻细胞内蛋白稳态网络，意味着负责生产和确保胶原蛋白完整性的机器，可能会带来巨大的好处。我们提出了一个针对胶原蛋白病的以蛋白稳态为重点的观点，强调了在了解如何在疾病中破坏胶原蛋白稳态的机制方面取得的进展。在平行下，