title: Disruption of zinc homeostasis and the pathogenesis of senile dementia.
abstract: Zinc (Zn) is an essential trace element that is abundantly present in the brain. Although Zn plays crucial roles in learning and memory, numerous studies have indicated that the disruption of Zn homeostasis, namely both depletion and excess Zn, causes severe damage to neurons and is linked with various neurodegenerative diseases including Alzheimer's disease and vascular dementia. Here, we review the current understanding of the role of Zn in the pathogenesis of these neurodegenerative diseases. Based on our findings and other numerous studies, Zn acts as a contributor to Alzheimer's disease in the oligomerization, and as a protector in the neurotoxicity of Alzheimer's β-amyloid protein. Furthermore, Zn plays a central role in ischemia-induced neuronal death and the pathogenesis of vascular dementia. Involvement of Ca(2+) dyshomeostasis and endoplasmic reticulum (ER) stress in the mechanism of Zn-induced neurotoxicity are suggested. We also discuss the possible role of carnosine (β-alanyl histidine), a dipeptide that is present in the brain, as a protective substance for neuronal injury.
authors.affiliation: Department of Bio-Analytical Chemistry, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. makawa@musashino-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.forename: Hironari
authors.initials: H
authors.lastname: Koyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Konoha
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohkawara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sadakane
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D015140:Dementia, Vascular / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015032:Zinc