Rani Shikha, Tuteja Minkal
Biophysics Department, University of Delhi, South Campus, Benito Juarez Road, New Delhi-110021, India.
Department of Pharmacy, Panipat Institute of Engineering and Technology, India.
Curr Protein Pept Sci. 2025 Jan 27. doi: 10.2174/0113892037338028241230092414.
The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.
蛋白质的三维结构是通过新生多肽链在体内的折叠形成的，这在很大程度上得益于分子伴侣，分子伴侣对于决定蛋白质的功能至关重要。除了协助折叠过程外，分子伴侣还将错误折叠的蛋白质作为降解目标，在细胞内充当一种质量控制系统。蛋白质折叠缺陷与多种临床病症有关，包括神经退行性疾病和代谢紊乱。现在人们已经清楚地认识到，帕金森病、阿尔茨海默病、亨廷顿病、肌萎缩侧索硬化症和克雅氏病等神经退行性疾病的发病机制有一个共同的机制：错误折叠的蛋白质积累，这些蛋白质聚集并对细胞产生毒性。在分子伴侣家族中，热休克蛋白（HSPs）在细胞应激反应中高度表达，在防止蛋白质聚集方面发挥着关键作用。特定的分子伴侣，特别是热休克蛋白，现在被认为在阻止这些情况下错误折叠蛋白质的积累和聚集方面至关重要。因此，这些分子伴侣越来越被视为治疗蛋白质聚集相关疾病的有前景的药理学靶点。这篇综述重点介绍了探索特定分子伴侣在以错误折叠蛋白质积累为特征的疾病中的潜在作用的研究。
