title: 6-Ethyl-N,N'-bis(3-hydroxyphenyl)[1,3,5]triazine-2,4-diamine (RS-0466) enhances the protective effect of brain-derived neurotrophic factor on amyloid beta-induced cytotoxicity in cortical neurones.
abstract: Amyloid beta peptide in the senile plaques of patients with Alzheimer's disease is considered to be responsible for the pathology of Alzheimer's disease. We have previously reported that 6-ethyl-N,N'-bis(3-hydroxyphenyl)[1,3,5]triazine-2,4-diamine, RS-0466, is capable of significantly inhibiting amyloid beta-induced cytotoxicity in HeLa cells. To determine various profiles of RS-0466, we investigated whether RS-0466 would enhance the neuroprotective effect of brain-derived neurotrophic factor on amyloid beta(1-42)-induced cytotoxicity in rat cortical neurones. Consistent with previous observations, brain-derived neurotrophic factor ameliorated amyloid beta(1-42)-induced cytotoxicity. Furthermore, co-application of RS-0466 enhanced the neuroprotective effect of brain-derived neurotrophic factor. RS-0466 also reversed amyloid beta(1-42)-induced decrease of brain-derived neurotrophic factor-triggered phosphorylated Akt. These results raise the possibility that RS-0466 or one of its derivatives has potential to enhance the neuroprotective effect of brain-derived neurotrophic factor, and could serve as a therapeutic agent for patients with Alzheimer's disease.
authors.affiliation: Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Takekazu
authors.initials: T
authors.lastname: Kubo
authors.forename: Satoko
authors.initials: S
authors.lastname: Nishimura
authors.forename: Takako
authors.initials: T
authors.lastname: Murasugi
authors.forename: Isao
authors.initials: I
authors.lastname: Kaneko
authors.forename: Masaki
authors.initials: M
authors.lastname: Meguro
authors.forename: Shinji
authors.initials: S
authors.lastname: Marumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogen
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koyama
authors.forename: Tomiichiro
authors.initials: T
authors.lastname: Oda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakagami
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000627:therapeutic use*
chemical_list: C475699:6-ethyl-N,N'-bis(3-hydroxyphenyl)(1,3,5)triazine-2,4-diamine; D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014227:Triazines; C075222:amyloid beta-protein (1-42)