Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6602-6607. doi: 10.1073/pnas.1821534116. Epub 2019 Mar 20.
UV light and other factors damage crystallin proteins in the eye lens, resulting in cataracts that scatter light and affect vision. Little information exists about protein structures within these disease-causing aggregates. We examined postmortem lens tissue from individuals with and without cataracts using 2D infrared (2DIR) spectroscopy. Amyloid β-sheet secondary structure was detected in cataract lenses along with denatured structures. No amyloid structures were found in lenses from juveniles, but mature lenses with no cataract diagnosis also contained amyloid, indicating that amyloid structures begin forming before diagnosis. Light scatters more strongly in regions with amyloid structure, and UV light induces amyloid β-sheet structures, linking the presence of amyloid structures to disease pathology. Establishing that age-related cataracts involve amyloid structures gives molecular insight into a common human affliction and provides a possible structural target for pharmaceuticals as an alternative to surgery.
紫外线和其他因素会破坏眼睛晶状体中的晶体蛋白，导致白内障，使光线散射，影响视力。关于这些致病聚集体中的蛋白质结构，目前信息有限。我们使用二维红外（2DIR）光谱技术检查了有和没有白内障的个体的死后晶状体组织。在白内障晶状体中检测到淀粉样 β-折叠二级结构以及变性结构。在幼年晶状体中未发现淀粉样结构，但无白内障诊断的成熟晶状体也含有淀粉样物质，表明淀粉样结构在诊断前就开始形成。有淀粉样结构的区域光散射更强，紫外线会诱导淀粉样 β-折叠结构，将淀粉样结构的存在与疾病病理联系起来。确定与年龄相关的白内障涉及淀粉样结构，这为常见的人类疾病提供了分子层面的深入了解，并为药物提供了一个可能的结构靶点，作为手术的替代方案。
