Abstract
Synaptic zinc ions (Zn(2+)) 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 Zn(2+)-induced neurotoxicity that leads to the pathogenesis of these neuronal diseases. Zn(2+)-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 Zn(2+)-induced neurotoxicity. GT1-7 cells were also used to search for substances that prevent Zn(2+)-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 Zn(2+)-induced cytotoxicity and discussed the prospects for the future therapeutic applications of this dipeptide for neurodegenerative diseases and dementia.