title: Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.
abstract: Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases.
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. makawa@musashino-u.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.forename: Keiko
authors.initials: K
authors.lastname: Konoha-Mizuno
authors.forename: Miwako
authors.initials: M
authors.lastname: Mori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sadakane
authors.forename: Hironari
authors.initials: H
authors.lastname: Koyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohkawara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D000861:Anserine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002460:Cell Line; D015140:Dementia, Vascular / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D002336:Carnosine; D000861:Anserine; D015032:Zinc