Neuroprotective mechanism of carnosine against zinc-induced neurotoxicity: a possible drug for vascular dementia

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Musashino University
• Principal Investigator: Kawahara Masahiro 武蔵野大学, 薬学研究所, 教授 (40224828)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経毒性 / 亜鉛 / 銅 / カルシウム / 小胞体ストレス / アルツハイマー病 / プリオン病 / 老年性認知症

Outline of Final Research Achievements

Carnosine (β-alanyl histidine) is a small dipeptide abundantly present in the muscloes and brains. Carnosine has numerous beneficial characteristics, including the maintenance of the acid-base balance, antioxidant, metal chelating, anti-crosslinking, and anti-glycation activities. We investigated the neuroprotective effects of carnosine and the related compounds, and found that carnosine attenuated zinc-induced neurodegeneration, which plays central roles in the pathogenesis of vascular dementia. Furthermore, carnosine and its analogue anserine inhibited zinc-induced endoplasmic reticulum (ER)-stress, and attenuated the neurotoxicity induced by ER-stress inducers such as thapsigargin. We developed a convenient method to quantify the amount of carnosine using HPLC equipped with the carbon column, and investigated the amount of carnosine and anserine in various foods or in muscles of Thoroughbred horses. Our results are useful in the development of drugs for vascular dementia.

Free Research Field

神経生化学、分析化学