Abstract
Our study was performed to assess the hypothesis that prolyl endopeptidase (PEP) would be functionally involved in the senescence-accelerated amyloid formation and that long-term inhibition of prolyl endopeptidase would suppress the progression of Aβ-like deposition in the hippocampus of the senescence-accelerated mouse (SAM). Granular structures of Aβ-LI were observed in the hippocampus and around cerebral microvessels of the SAM after immunohistochemical staining with specific anti-Aβ antibody. Repeated treatment of the SAM with Y-29794 (1, 10, 20 mg/kg, p.o.), a specific inhibitor of prolyl endopeptidase, significantly reduced the number and density of Aβ-positive granular structures in the hippocampus of the SAM, after digital image analysis with NIH Image software. Furthermore, the characteristic biphasic distribution of the digitized density of the granules was significantly modulated after the treatment with Y-29794. These results suggest that chronic treatment of the SAM with Y-29794, a nonpeptide inhibitor of prolyl endopeptidase, prevents the progression of Aβ-like deposition in the hippocampus of the SAM.
Footnotes
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Send reprint requests to: Dr. Tohru Nakajima, Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., 955 Koiwai Yoshitomi-cho, Chikujo-gun, Fukuoka 871, Japan.
- Abbreviations:
- Aβ
- β-amyloid peptide
- Aβ-LI
- β-amyloid peptide-like immunoreactivity
- APP
- β-amyloid precursor proteins
- PEP
- prolyl endopeptidase
- SAM
- senescence-accelerated mouse
- TBS
- Tris-buffered saline
- AD
- Alzheimer’s disease
- Received March 18, 1997.
- Accepted June 26, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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