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Nobuhisa Iwata,1Satoshi Tsubuki,1Yoshie Takaki,1Keiro Shirotani,1Bao Lu,2Norma P. Gerard,2Craig Gerard,2Emi Hama,1Hahn-Jun Lee,1Takaomi C. Saido1*
Amyloid peptide (A), the pathogenic agent of Alzheimer's
disease (AD), is a physiological metabolite in the brain. We examinedthe role of neprilysin, a candidate A-degrading peptidase, inthe
metabolism using neprilysin gene-disrupted mice. Neprilysindeficiency
resulted in defects both in the degradation of exogenouslyadministered
A and in the metabolic suppression of the endogenousA levels in
a gene dose-dependent manner. The regional levelsof A in the
neprilysin-deficient mouse brain were in the distinctorder of
hippocampus, cortex, thalamus/striatum, and cerebellum,where
hippocampus has the highest level and cerebellum the lowest,correlating with the vulnerability to A deposition in brainsof
humans with AD. Our observations suggest that even partialdown-regulation of neprilysin activity, which could be causedby aging,
can contribute to AD development by promoting A accumulation.
1 Laboratory for Proteolytic Neuroscience,
RIKEN Brain Science Institute, Wako-shi 351-0198 Japan.
2 Department of Pediatrics and Medicine, Harvard
Medical School, Boston, MA 02115, USA.
*
To whom correspondence should be addressed. E-mail:
saido{at}brain.riken.go.jp
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|Abstract »|Full Text »|PDF »
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J. Biol. Chem.
279, 56004-56013
|Abstract »|Full Text »|PDF »
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V. Laporte, Y. Lombard, R. Levy-Benezra, C. Tranchant, P. Poindron, and J.-M. Warter (2004)
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|Abstract »|Full Text »|PDF »
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279, 30259-30264
|Abstract »|Full Text »|PDF »
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164, 1425-1434
|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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278, 49448-49458
|Abstract »|Full Text »|PDF »
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278, 37314-37320
|Abstract »|Full Text »|PDF »
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J. Biol. Chem.
278, 23221-23226
|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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by Neprilysin
peptide (A
