Protective substances against zinc-induced neuronal death after ischemia: carnosine as a target for drug of vascular type of dementia.
Recent studies have indicated the significance of zinc in neurodegeneration after transient global ischemia. After ischemia, excess glutamate and zinc, which are released in the synaptic clefts, cause the apoptotic death of the target neurons, and finally lead the pathogenesis of vascular type of dementia. Considering the removal of zinc using zinc-sensitive chelators was effective in the prevention of neuronal death after transient global ischemia, it is highly possible that substances which protect against zinc-induced neuronal death will become a candidate for drugs of vascular type of dementia. Based on this 'zinc hypothesis', we have searched for such substances among various agricultural products including fruits, vegetables, and fishes using our developed in vitro screening system. Among tested, we found that carnosine (beta-alanyl histidine) protected against zinc-induced death of cultured neurons, and have applied for the patent as a drug of ischemia-induced neuronal death and the treatment/prevention for vascular type of dementia (application No. 2006-145857) in Japan. Here, we review the perspective of protective substances of zinc-induced neuronal death as a drug of vascular type of dementia based on our studies and other numerous studies.
Kawahara
Masahiro
M
Department of Analytical Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-cho, Nobeoka-city, Miyazaki, 882-8508, Japan. kawamasa@phoenix.ac.jp
Konoha
Keiko
K
Nagata
Tetsuya
T
Sadakane
Yutaka
Y
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002336:Carnosine / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015032:Zinc / Q000633:toxicity*
D018696:Neuroprotective Agents; D002336:Carnosine; D015032:Zinc