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

Pharmacol Toxicol. 2003 Dec;93(6):264-8. doi: 10.1111/j.1600-0773.2003.pto930603.x.

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.

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Microtubule-Associated Proteins / drug effects*
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Triazines / therapeutic use*

Substances

  • 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)