A novel neuroprotective compound FR901459 with dual inhibition of calcineurin and cyclophilins.

Abstract

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. In our study, we show that the marked neuroprotection of the new immunosuppressant FR901495 in forebrain ischemia is due not only to inhibition of calcineurin, but also to protection against mitochondrial damage caused by mitochondrial permeability transition pore formation through cyclophilin D, one of the prolyl cis/trans isomerase family members. These findings shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.

• Authors: H Uchino, S Morota, T Takahashi, Y Ikeda, Y Kudo, N Ishii, B K Siesjö, F Shibasaki
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 96 Pg. 157-62 ( 2006) ISSN: 0065-1419 [Print] Austria
• PMID: 16671446 (Publication Type: Journal Article)

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Neuroprotective Agents
• FR 901459
• Cyclosporine
• Calcineurin
• Cyclophilins

Topics

• Animals
• Brain Injuries (complications, drug therapy, metabolism)
• Brain Ischemia (complications, drug therapy, metabolism)
• Calcineurin
• Cyclophilins
• Cyclosporine
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Mitochondrial Membrane Transport Proteins (drug effects, metabolism)
• Mitochondrial Permeability Transition Pore
• Neuroprotective Agents (administration & dosage)
• Prosencephalon (drug effects, injuries, metabolism)
• Rats
• Rats, Wistar
• Treatment Outcome