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.
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.
Kubo
Takekazu
T
Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Nishimura
Satoko
S
Murasugi
Takako
T
Kaneko
Isao
I
Meguro
Masaki
M
Marumoto
Shinji
S
Kogen
Hiroshi
H
Koyama
Kazuo
K
Oda
Tomiichiro
T
Nakagami
Yasuhiro
Y
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*
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)