The Role of Zinc in the Development of Vascular Dementia and Parkinson’s Disease and the Potential of Carnosine as Their Therapeutic Agent

Author:

Mizuno Dai1ORCID,Kawahara Masahiro2ORCID,Konoha-Mizuno Keiko1,Hama Ryoji1,Ogawara Terumasa1

Affiliation:

1. Department of Forensic Medicine, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-shi 990-9585, Yamagata, Japan

2. Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi 202-8585, Tokyo, Japan

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.

Funder

Ministry of Education, Culture, Sports, Science, and Technology of Japan

Publisher

MDPI AG

Reference137 articles.

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