Abstract:
Cataract is one of the leading causes of blindness worldwide. Till date, the only solution for cataracts is surgery, which is a resource-intensive solution. A much simpler solution is to find a potential drug that could inhibit aggregation. It is well established that nonamyloid aggregates of eye lens protein result in cataract. γD-Crystallin, a thermodynamically stable protein, is one of the most abundant proteins in the core of the eye lens and is found to aggregate under stress conditions, leading to the cataract. It has also been found that in cataractous lens, the concentration of metals like copper is elevated significantly as compared to healthy eye lens, suggesting their role in inducing aggregation. In our present study, aggregation of γD-Crystallin was carried out in the presence of Cu (II). Using techniques like turbidity assay, CD spectroscopy, ANS binding assay, and microscopic studies like TEM, it could be confirmed that protein aggregates in the presence of Cu (II) and the nature of aggregates is amorphous. Various polyphenols were tested to suppress aggregation of the protein. Quercetin was observed to be the most efficient. To overcome the problems associated with the delivery of polyphenols, such as solubility and bioavailability, quercetin was encapsulated in two types of nanocarriers. Their characterization was done using TEM, DLS, and other techniques. The potency of quercetin-loaded CS-TPP/CS-PLGA NPs as inhibitors of γD-Crystallin aggregation was confirmed by various experiments.
摘要:
白内障是世界范围内导致失明的主要原因之一。直到日期,白内障的唯一解决方案是手术,这是一个资源密集型的解决方案。一个简单得多的解决方案是找到一种可以抑制聚集的潜在药物。已经确定眼晶状体蛋白的非淀粉样蛋白聚集体导致白内障。γD-晶体蛋白,热力学稳定的蛋白质,是眼睛晶状体核心中最丰富的蛋白质之一,被发现在压力条件下聚集,导致白内障。还发现,在白内障晶状体中,与健康的眼睛晶状体相比,铜等金属的浓度显着升高,表明它们在诱导聚集中的作用。在我们目前的研究中,γD-晶体蛋白的聚集在Cu(II)存在下进行。使用浊度测定等技术,CD光谱学,ANS结合测定,和像透射电镜这样的微观研究,可以证实,在Cu(II)存在下的蛋白质聚集体和聚集体的性质是无定形的。测试了各种多酚以抑制蛋白质的聚集。观察到槲皮素是最有效的。为了克服与多酚递送相关的问题,如溶解度和生物利用度,槲皮素被封装在两种类型的纳米载体中。它们的表征是使用TEM完成的,DLS,和其他技术。通过各种实验证实了负载槲皮素的CS-TPP/CS-PLGANP作为γD-晶体蛋白聚集抑制剂的效力。