Molecular Immunology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
Sci Rep. 2018 Nov 23;8(1):17283. doi: 10.1038/s41598-018-35645-4.
Amyloids are highly organized fibril aggregates arise from inappropriately folded form of the protein or polypeptide precursors under both physiological as well as simulated ambience. Amyloid synthesis is a multistep process that involves formation of several metastable intermediates. Among various intermediate species, the as-formed soluble oligomers are extremely toxic to the neuronal cells. In the present study, we evaluated cyclosporine A (CsA), an undecapeptide, for its potential to prevent aggregation of model protein ovalbumin (OVA). In an attempt to elucidate involved operative mechanism, the preliminary studies delineate that CsA affects both primary nucleation as well as other secondary pathways involved in OVA fibrillation process. By its specific interaction with amyloid intermediates, the cyclic peptide CsA seems to regulate the lag phase of the fibrillation process in concentration dependent manner. The present study further suggests that exposure to CsA during lag phase ensues in reversal of OVA fibrillation process. On the contrary, mature OVA fibril remained impervious to the CsA treatment. The cyclic undecapeptide CsA was also found to successfully alleviate amyloid induced toxicity in neuroblastoma cells.
淀粉样蛋白是由生理和模拟环境下蛋白质或多肽前体的错误折叠形式形成的高度有序的纤维状聚集物。淀粉样蛋白的合成是一个多步骤的过程，涉及到形成几个亚稳态中间产物。在各种中间产物中，形成的可溶性寡聚物对神经元细胞具有极强的毒性。在本研究中，我们评估了环孢素 A（CsA），一种十一肽，以评估其预防模型蛋白卵清蛋白（OVA）聚集的潜力。为了阐明涉及的作用机制，初步研究表明 CsA 影响 OVA 纤维化过程中的初级成核以及其他次级途径。通过与淀粉样中间产物的特异性相互作用，环肽 CsA 似乎以浓度依赖的方式调节纤维化过程的延滞期。本研究进一步表明，在延滞期接触 CsA 会导致 OVA 纤维化过程的逆转。相反，成熟的 OVA 纤维对 CsA 处理仍然不敏感。还发现环状十一肽 CsA 可成功减轻神经母细胞瘤细胞中的淀粉样蛋白诱导的毒性。
