2001 Fiscal Year Final Research Report Summary
Development of the agents to stimulate neurotrophin synthesis -An approach for spinal cord regeneration-
| Project/Area Number |
11557111
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Aichi Bunkyo Women's College |
|---|
Principal Investigator |
FURUKAWA Yoshiko Aichi Bunkyo Women' s College, Professor, 教授 (20219108)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
新田 淳美 岐阜薬科大学, 薬学部, 助手 (20275093)
岩田 章子 愛知文教女子短期大学, 助教授 (20149503)
古川 昭栄 岐阜薬科大学, 薬学部, 教授 (90159129)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | immunosuppressive drugs / neurotrophic factors / spinal cord injury / neuroprotection / nerve regeneration / injury restoration / 免疫抑制剤 / イムノフィリンリガンド |
|---|
| Research Abstract |
Immunophilin ligands have been reported to possess neurotrophic activities including neurite-promoting activity in addition to well-known inimunosuppressive actions, but the mechanisms under the neurotrophic effects remain unknown. We presumed that immunophilin ligands show the neurotrophic actions by the regulation of synthesis of neurotrophic factors, and examined this possibility by in vitro and in vivo experiments. Immunophilin ligands, cyclosporin A and FK506, have been proved to stimulate synthesis of brain-derived neurotrophic factor (BDNF) and/or glial cell line-derived neurotrophic factor (GDNF) in cultured neurons and astrocytes or in adult rat brain, suggesting a possible use of immunophilin ligands as neuroprotective agents in some neurological disorders. However, the inimunosuppressive activity is disadvantageous for therapeutic use for general disorders. Therefore, we tried to find an active immunophilin ligand without immunpsuppressive activity by focusing the active structure of FK506 and cyclosporin A for binding to immunophilin protein. Dipeptides composed of hydrophobic aminiacid such as Leu-Ile, Pro-Leu or Pro-He that resemble to the active structure of immunosuppressive drugs, and can bind immunophilins. We examined these and their derivatives, and found the Leu-Ile dipeptide as active substances with neurotrophic factor synthesis stimulatory activity and without immunosuppressive activity." As Leu-Ile was considered to bean ideal agent for neuroregeneration, we applied it once a day for 30 days to the rats with spinal cord semi-transection. However, motor activity was not improved even 30 days after the administration. Much more investigation is necessary to evaluate the Leu-Ile activity on the spinal cord nerve regeneration. Particular points to examine are methods for administration and dosage of the drug.
|
