PDF(Pubmed)
Abstract：
Synaptic zinc ions (Zn2+) play an important role in the development of vascular dementia (VD) and Parkinson\'s disease (PD). In this article, we reviewed the current comprehension of the Zn2+-induced neurotoxicity that leads to the pathogenesis of these neuronal diseases. Zn2+-induced neurotoxicity was investigated by using immortalised hypothalamic neurons (GT1-7 cells). This cell line is useful for the development of a rapid and convenient screening system for investigating Zn2+-induced neurotoxicity. GT1-7 cells were also used to search for substances that prevent Zn2+-induced neurotoxicity. Among the tested substances was a protective substance in the extract of Japanese eel (Anguilla japonica), and we determined its structure to be like carnosine (β-alanylhistidine). Carnosine may be a therapeutic drug for VD and PD. Furthermore, we reviewed the molecular mechanisms that involve the role of carnosine as an endogenous protector and its protective effect against Zn2+-induced cytotoxicity and discussed the prospects for the future therapeutic applications of this dipeptide for neurodegenerative diseases and dementia.
摘要：
突触锌离子(Zn2+)在血管性痴呆(VD)和帕金森病(PD)的发生发展中起重要作用。在这篇文章中,我们回顾了目前对Zn2+诱导的神经毒性的理解，该毒性导致了这些神经元疾病的发病机制。通过使用永生化的下丘脑神经元（GT1-7细胞）研究了Zn2诱导的神经毒性。该细胞系可用于开发快速便捷的筛选系统，以研究Zn2诱导的神经毒性。GT1-7细胞也用于寻找防止Zn2+诱导的神经毒性的物质。在测试物质中有日本鳗鱼（Anguillajaponica）提取物中的保护性物质，我们确定其结构类似于肌肽（β-丙氨酰组氨酸）。肌肽可能是VD和PD的治疗药物。此外，我们综述了肌肽作为内源性保护剂的作用及其对Zn2+诱导的细胞毒性的保护作用的分子机制，并讨论了该二肽在神经退行性疾病和痴呆中的未来治疗应用前景。
