| Project/Area Number |
03454493
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
YOSHIMOTO Tadashi NAGASAKI UNIVERSITY, School of Pharm. Associate Professor, 薬学部, 助教授 (60088870)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥3,700,000 (Direct Cost: ¥3,700,000)
|
|---|
| Keywords | prolyl endopeptidase / peptidase / protease / Alzheimer's disease / protease II / プロテアーゼ / アルツハイマー症 / 脳 / プロテアーゼ2 / クローニング / 遺伝子組換え / プロリルエンドペプチダ-ゼ / クロ-ニング / 塩基配列決定 / プロテア-ゼII |
|---|
| Research Abstract |
The prolyl endopeptidase [EC 3.4.21.26] genes of Flavobacterium meningosepticum, A.hydrophila, and bovine brain, and protease II gene from E.coli were cloned. A high conservation of primary structure is observed among these four enzumes. Surprisingly, C-terminal regions of prolyl endopeptidase show significant homology to following proteins : pig and rat acyl-amino acid releasing enzymes, human protein 3P21, rat and human dipeptidyl aminopeptidases IV, yeast dipeptidyl aminopeptidase B, and X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. The amino acid residues of the catalytic triad are well conserved. These enzymes have also common characteristics on oligopeptides. Thus, presence of prolyl oligpeptidase family was proposed as a new family of serine endopeptidases.
Amyloid b/A4 peptide is one of the integral components that are typically manifested in senile plaques and cerebrovascular amyloids in the patients with Alzheimer's disease. I ascertained for the first time the distribution of prolyl endopeptidase in senescence accelerated mouse (SAM) by the immunostaining method. I also found that prolyl endopeptidase and amyloid b/A4 peptide distributed with close relationships in the hippocampus. These result suggest that prolyl endopeptidase is involved in the processes to form amyloid deposition in the brain of SAM.
|
