Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Affiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Biochim Biophys Acta Gen Subj. 2022 Feb;1866(2):130061. doi: 10.1016/j.bbagen.2021.130061. Epub 2021 Nov 22.
Protein aggregation is correlated with the onset and progression of protein misfolding diseases (PMDs). Inhibiting the generation of toxic aggregates of misfolded proteins has been proposed as a therapeutic approach for PMDs. Due to their unique properties, nanomaterials have been extensively investigated for their ability to inhibit protein aggregation and have shown great potential in the diagnosis and treatment of PMDs. However, the precise mechanisms by which nanomaterials interact with amyloidogenic proteins and the factors influencing these interactions remain poorly understood. Consequently, developing a rational design strategy for nanomaterials that target specific proteins in PMDs has been challenging. In this review, we elucidate the effects of nanomaterials on protein aggregation and describe the mechanisms through which nanomaterials interfere with protein aggregation. The major factors impacting protein-nanomaterial interaction such as size, charge, concentration, surface modification and morphology that can be rationally addressed to achieve the desired effects of nanomaterials on protein aggregation are summarized. The prospects and challenges to the clinical application of nanomaterials for the treatment of PMDs are also discussed.
蛋白质聚集与蛋白质错误折叠疾病(PMDs)的发病和进展有关。抑制错误折叠蛋白质的有毒聚集体的产生已被提议作为 PMD 的治疗方法。由于纳米材料具有独特的性质,因此已经广泛研究了它们抑制蛋白质聚集的能力,并在 PMD 的诊断和治疗中显示出巨大的潜力。然而,纳米材料与淀粉样蛋白的相互作用的确切机制以及影响这些相互作用的因素仍知之甚少。因此,开发针对 PMD 中特定蛋白质的纳米材料的合理设计策略一直具有挑战性。在这篇综述中,我们阐明了纳米材料对蛋白质聚集的影响,并描述了纳米材料干扰蛋白质聚集的机制。总结了影响蛋白质-纳米材料相互作用的主要因素,如大小、电荷、浓度、表面修饰和形态,可以合理地解决这些因素,以达到纳米材料对蛋白质聚集的预期效果。还讨论了纳米材料在治疗 PMD 中的临床应用的前景和挑战。