1. Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.
- Author
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Mizuno D, Konoha-Mizuno K, Mori M, Sadakane Y, Koyama H, Ohkawara S, and Kawahara M
- Subjects
- Animals, Antioxidants pharmacology, Cell Line, Dementia, Vascular drug therapy, Dementia, Vascular metabolism, Dementia, Vascular pathology, Mice, Neurons drug effects, Neurons metabolism, Neurons pathology, Zinc metabolism, Anserine pharmacology, Carnosine pharmacology, Dementia, Vascular chemically induced, Endoplasmic Reticulum Stress drug effects, Neuroprotective Agents pharmacology, Zinc toxicity
- 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.
- Published
- 2015
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