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.
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Authors | Takekazu Kubo, Satoko Nishimura, Takako Murasugi, Isao Kaneko, Masaki Meguro, Shinji Marumoto, Hiroshi Kogen, Kazuo Koyama, Tomiichiro Oda, Yasuhiro Nakagami |
Journal | Pharmacology & toxicology
(Pharmacol Toxicol)
Vol. 93
Issue 6
Pg. 264-8
(Dec 2003)
ISSN: 0901-9928 [Print] Denmark |
PMID | 14675459
(Publication Type: Journal Article)
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Chemical References |
- 6-ethyl-N,N'-bis(3-hydroxyphenyl)(1,3,5)triazine-2,4-diamine
- Amyloid beta-Peptides
- Microtubule-Associated Proteins
- Neuroprotective Agents
- Peptide Fragments
- Triazines
- amyloid beta-protein (1-42)
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Topics |
- Amyloid beta-Peptides
(antagonists & inhibitors, toxicity)
- Animals
- Cells, Cultured
- Cerebral Cortex
(drug effects, metabolism)
- Microtubule-Associated Proteins
(drug effects)
- Neuroprotective Agents
(therapeutic use)
- Peptide Fragments
(antagonists & inhibitors, toxicity)
- Rats
- Rats, Sprague-Dawley
- Triazines
(therapeutic use)
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