The activity and mRNA expression of β-secretase, cathepsin D, and cathepsin B in the brain of senescence-accelerated mouse.
The senescence accelerated mouse prone 8 (SAMP8), an animal model of Alzheimer's disease, has amyloid-β deposition in the brain. This study showed that β-secretase activity increased age-dependently in cerebral cortex of SAMP8 and SAMP8's control, SAM resistant/1 (SAMR1), and was higher in the hippocampus of SAMP8 than that of age-matched SAMR1. Cathepsin D activity also increased age-dependently in the cerebral cortex of SAMP8. There was no significant difference between SAMP8 and SAMR1 with regards to activity of cathepsin B. β-secretase activity had a positive correlation with cathepsin D activity in the cerebral cortex of SAMR1 and SAMP8. There was a tendency toward decreased mRNA expression of BACE1, cathepsin D, and cathepsin B in the hippocampus of SAMR1 and SAMP8 with aging. mRNA expression of cathepsin B was elevated significantly in the cerebral cortex of SAMP8 at 2 and 6 months of age compared to that of age-matched SAMR1, and similarly so was cathepsin D at 2 months. This data showed there was no correlation between mRNA expression and activity of β-secretase, cathepsin D, and cathepsin B in the brain of SAMR1 and SAMP8 with age. These findings also indicate it was cathepsin D, not cathepsin B, that contributed to β-secretase activity and the increased amyloid-β production in the SAMP8 brain. In addition, it was necessary to take into account the target selectivity of BACE1 and cathepsin D, not necessary to detect the mRNA expression, when SAMP8 was used as an animal model to determine the effect of β-secretase inhibitor.
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Jin-Wu
JW
Zhou
Xiao-Rui
XR
Cheng
Jun-Ping
JP
Cheng
Wen-Xia
WX
Zhou
Yong-xiang
YX
Zhang
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism*; D002401:Cathepsin B / Q000235:genetics*; D002402:Cathepsin D / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D002401:Cathepsin B; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D002402:Cathepsin D