RT Journal Article
SR Electronic
T1 Prevention of Amyloid-Like Deposition by a Selective Prolyl Endopeptidase Inhibitor, Y-29794, in Senescence-Accelerated Mouse
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 328
OP 335
VO 283
IS 1
A1 Akira Kato
A1 Atsushi Fukunari
A1 Yoko Sakai
A1 Tohru Nakajima
YR 1997
UL http://jpet.aspetjournals.org/content/283/1/328.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics