Ben-Shushan Shira, Miller Yifat
Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Be'er Sheva 84105, Israel.
Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
J Phys Chem B. 2021 Mar 25;125(11):2796-2811. doi: 10.1021/acs.jpcb.0c11151. Epub 2021 Feb 11.
Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by deposits of amyloid proteins. The homeostasis of metal ions is crucial for the normal biological functions in the brain. However, in AD and PD, the imbalance of metal ions leads to formation of amyloid deposits. In the past four decades, there has been extensive effort to design compound agents than can chelate metal ions with the aim of preventing the formation of the amyloid deposits. Unfortunately, the compounds to date that were designed were not successful candidates to be used in clinical trials. Neuropeptides are small molecules that are produced and released by neurons. It has been shown that neuropeptides have neuroprotective effects in the brain and reduce the formation of amyloid deposits. This Review Article is focused on the function of neuropeptides as metal chelators. Experimental and computational studies demonstrated that neuropeptides could bind metal ions, such as Cu and Zn. This Review Article provides perspectives and initiates future studies to investigate the role of neuropeptides as metal chelators in neurodegenerative diseases.
神经退行性疾病，如阿尔茨海默病（AD）和帕金森病（PD），其特征是淀粉样蛋白沉积。金属离子的稳态对于大脑中的正常生物学功能至关重要。然而，在AD和PD中，金属离子的失衡会导致淀粉样沉积物的形成。在过去的四十年里，人们付出了巨大努力来设计能够螯合金属离子的复合剂，以防止淀粉样沉积物的形成。不幸的是，迄今为止设计的化合物都不是可用于临床试验的成功候选物。神经肽是由神经元产生和释放的小分子。研究表明，神经肽在大脑中具有神经保护作用，并能减少淀粉样沉积物的形成。这篇综述文章聚焦于神经肽作为金属螯合剂的功能。实验和计算研究表明，神经肽可以结合金属离子，如铜和锌。这篇综述文章提供了观点，并开启了未来的研究，以探讨神经肽作为金属螯合剂在神经退行性疾病中的作用。
