Sehra Naina, Parmar Rajesh, Jain Rahul
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Sector 67, S. A. S. Nagar Punjab 160062 India
RSC Med Chem. 2024 Dec 31. doi: 10.1039/d4md00729h.
Aberrant protein misfolding and accumulation is considered to be a major pathological pillar of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Aggregation of amyloid-β (Aβ) peptide leads to the formation of toxic amyloid fibrils and is associated with cognitive dysfunction and memory loss in Alzheimer's disease (AD). Designing molecules that inhibit amyloid aggregation seems to be a rational approach to AD drug development. Over the years, researchers have utilized a variety of therapeutic strategies targeting different pathways, extensively studying peptide-based approaches to understand AD pathology and demonstrate their efficacy against Aβ aggregation. This review highlights rationally designed peptide/mimetics, including structure-based peptides, metal-peptide chelators, stapled peptides, and peptide-based nanomaterials as potential amyloid inhibitors.
异常的蛋白质错误折叠和积累被认为是神经退行性疾病（包括阿尔茨海默病和帕金森病）的主要病理支柱。淀粉样β（Aβ）肽的聚集导致有毒淀粉样纤维的形成，并与阿尔茨海默病（AD）中的认知功能障碍和记忆丧失有关。设计抑制淀粉样蛋白聚集的分子似乎是AD药物开发的合理方法。多年来，研究人员利用了多种针对不同途径的治疗策略，广泛研究基于肽的方法以了解AD病理学并证明其对Aβ聚集的疗效。本综述重点介绍了合理设计的肽/模拟物，包括基于结构的肽、金属-肽螯合剂、环肽和基于肽的纳米材料作为潜在的淀粉样蛋白抑制剂。
