Division of Otolaryngology, Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
Brain Res Bull. 2010 Jan 15;81(1):12-24. doi: 10.1016/j.brainresbull.2009.09.015.
Conformational diseases, a general term comprising more than 40 disorders are caused by the accumulation of unfolded or misfolded proteins. Improper protein folding (misfolding) as well as accrual of unfolded proteins can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The gradual accumulation of protein aggregates and the acceleration of their formation by stress explain the characteristic late or episodic onset of the diseases. The best studied in this group are neurodegenerative diseases and amyloidosis accompanied by the deposition of a specific aggregation-prone proteins or protein fragments and formation of insoluble fibrils. Amyloidogenic protein accumulation often occurs in the brain tissues, e.g. in Alzheimer's disease with the deposition of amyloid-beta and Tau, in scrapie and bovine spongiform encephalopathy with the accumulation of prion protein, in Parkinson's disease with the deposition of alpha-synuclein. Other examples of amyloid proteins are transthyretin, immunoglobulin light chain, gelsolin, etc. In addition to the brain, the accumulation of unfolded or misfolded proteins leading to pathology takes place in a wide variety of organs and tissues, including different parts of the eye. The best studied ocular conformational diseases are cataract in the lens and retinitis pigmentosa in the retina, but accumulation of misfolded proteins also occurs in other parts of the eye causing various disorders. Furthermore, ocular manifestation of systemic amyloidosis often causes the deposition of amyloidogenic proteins in different ocular tissues. Here we present the data regarding naturally unfolded and misfolded proteins in eye tissues, their structure-function relationships, and molecular mechanisms underlying their involvement in diseases. We also summarize the etiology of ocular conformational diseases and discuss approaches to their treatment.
构象疾病是一个广义术语，包含 40 多种疾病，是由未折叠或错误折叠的蛋白质积累引起的。蛋白质折叠不当（错误折叠）以及未折叠蛋白质的积累会导致无序（无定形）或有序（淀粉样纤维）聚集物的形成。蛋白质聚集物的逐渐积累以及压力加速其形成，解释了这些疾病特征性的晚期或偶发性发作。在这组疾病中，研究得最多的是神经退行性疾病和淀粉样变性，伴有特定聚集倾向的蛋白质或蛋白质片段的沉积和不溶性纤维的形成。淀粉样蛋白的积累通常发生在脑组织中，例如阿尔茨海默病中β淀粉样蛋白和 Tau 的沉积，克雅氏病和牛海绵状脑病中朊病毒蛋白的积累，帕金森病中α-突触核蛋白的沉积。其他淀粉样蛋白的例子有转甲状腺素蛋白、免疫球蛋白轻链、凝胶蛋白等。除了大脑，导致病理学的未折叠或错误折叠蛋白质的积累也发生在各种各样的器官和组织中，包括眼睛的不同部位。研究得最多的眼部构象疾病是晶状体的白内障和视网膜的色素性视网膜炎，但错误折叠蛋白的积累也发生在眼睛的其他部位，导致各种疾病。此外，系统性淀粉样变性的眼部表现通常导致淀粉样蛋白在不同的眼部组织中沉积。在这里，我们介绍了眼部组织中天然无规卷曲和错误折叠的蛋白质、它们的结构-功能关系以及它们参与疾病的分子机制的数据。我们还总结了眼部构象疾病的病因，并讨论了治疗方法。
