Journal of Clinical Toxicology
Open Access

Abstract

Zinc Neurotoxicity and the Pathogenesis of Vascular-Type Dementia: Involvement of Calcium Dyshomeostasis and Carnosine

Hironari Koyama, Keiko Konoha, Yutaka Sadakane, Susumu Ohkawara and Masahiro Kawahara

Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia. We found that GT1-7 cells (immortalized hypothalamic neurons) are more vulnerable to zinc-induced neurotoxicity than other cultured neuronal cells are. Further, we investigated the molecular mechanisms of Zn-induced neurotoxicity in vitro using GT1-7 cells. Pharmacological evidence based on our own results and those of numerous other studies has indicated the significance of calcium dyshomeostasis in the mechanisms of Zn-induced neuronal injury. We developed a screening system for substances, which prevent Zn-induced neurotoxicity, with the aim of identifying a treatment for vascular-type dementia. Here, we review in detail the characteristics and mechanisms of Zn-induced neuronal death in relation to calcium homeostasis. The potential role of carnosine (ß-alanyl histidine), a dipeptide present in the brain as an endogenous protective substance, in neuronal injury is also discussed.