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Clay-Polymer Nanocomposites Mediated Inhibition of Protein Aggregation: Possible Role in the Prevention of Proteinopathies
Protein & Peptide Letters ( IF 1.6 ) Pub Date : 2023-10-15 , DOI: 10.2174/0109298665274059231002071951
Romana Parveen 1 , Sher Ali 1 , Sadaf Fatima 1
Affiliation  

Background: The transformation of proteins from their native conformation into highly ordered fibrillar structures due to their misfolding and aggregation under particular conditions are described as beta-sheet enriched amyloid fibrils. The accumulation of these fibrils in different body parts is the major cause of several neurological and non-neurological conditions (proteinopathies). Objectives: To prevent these proteinopathies, inhibition of protein aggregation is considered a promising strategy. Therefore, in this study, we synthesized montmorillonite (MMT) based poly- orthophenylenediamine (PoPD) nanocomposites (NCs) and characterized their size and morphology due to their remarkable biological properties. Further, the effect of these nanocomposites on inhibition of fibril formation was assessed. Methods: These nanocomposites were evaluated for their anti-amyloidogenic potential on two model proteins of amyloidopathies, i.e., human lysozyme and human serum albumin (HL & HSA), by using several biophysical methods, such as Thioflavin T (ThT) and 1-anilino-8-naphthalene sulfonate (ANS) fluorescence, congo red dye binding assay (CR). Secondary structural content was evaluated by Circular dichroism (CD) spectroscopy. Results: Results demonstrated that synthesized nanocomposites significantly inhibited fibril formation in dose-dependent manner that corresponds to their ability to arrest fibrillation. It is suggested that they may adsorb proteins to protect them against aggregation when they are subjected to aggregating conditions. Conclusion: This study offers an opportunity to understand the mechanism of inhibition of fibril formation by nanocomposites, showing that they inhibit amyloid formation and amyloid diseases. Thus, the study concludes that these nanocomposites are promising candidates as therapeutic molecules for proteinopathies and are envisaged to enrich the area of personalized medicine, augmenting the human healthcare system.

中文翻译:

粘土聚合物纳米复合材料介导的蛋白质聚集抑制:在预防蛋白质病中的可能作用

背景:蛋白质由于在特定条件下错误折叠和聚集而从其天然构象转变为高度有序的纤维结构,被描述为富含β折叠的淀粉样原纤维。这些原纤维在身体不同部位的积累是多种神经系统和非神经系统疾病(蛋白质病)的主要原因。目的:为了预防这些蛋白质病,抑制蛋白质聚集被认为是一种有前途的策略。因此,在本研究中,我们合成了基于蒙脱土(MMT)的聚邻苯二胺(PoPD)纳米复合材料(NC),并由于其卓越的生物学特性而表征了它们的尺寸和形态。此外,还评估了这些纳米复合材料对原纤维形成的抑制作用。方法:通过使用硫磺素 T (ThT) 和 1-苯胺基等多种生物物理方法,评估这些纳米复合材料对淀粉样蛋白病的两种模型蛋白,即人溶菌酶和人血清白蛋白 (HL 和 HSA) 的抗淀粉样变潜力。 -8-萘磺酸盐(ANS)荧光,刚果红染料结合测定(CR)。通过圆二色性(CD)光谱评估二级结构含量。结果:结果表明,合成的纳米复合材料以剂量依赖性方式显着抑制原纤维形成,这与其阻止原纤维颤动的能力相对应。有人认为,当蛋白质处于聚集条件时,它们可能会吸附蛋白质以防止蛋白质聚集。结论:这项研究提供了了解纳米复合材料抑制原纤维形成的机制的机会,表明它们可以抑制淀粉样蛋白形成和淀粉样蛋白疾病。因此,该研究得出的结论是,这些纳米复合材料是作为蛋白质病治疗分子的有希望的候选者,并有望丰富个性化医疗领域,增强人类医疗保健系统。
更新日期:2023-10-15
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