2010 Fiscal Year Final Research Report
The role of M16 family metalloprotease in Alzheimer's disease
| Project/Area Number |
21700351
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
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| Research Institution | Kyoto University |
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Principal Investigator |
HIRAOKA Yoshinori Kyoto University, 医学研究科, 助教 (60397552)
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| Project Period (FY) |
2009 – 2010
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| Keywords | アルツハイマー病 / M16メタロプロテアーゼ / αセクレターゼ |
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| Research Abstract |
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the formation of amyloidβpeptide (Aβ) and their deposition in the brain as senile plaques. In the nonamyloidgenic pathway, the amyloid precursor protein (APP) is cleaved by theα-secretase within the Aβsequence. Proteinases of the ADAM family are the main candidates, but the underlying mechanism is not cleared. We have demonstrated that nardilysin (N-arginine dibasic convertase; NRDc), a metalloendopeptidase of M16 family, enhacesα-secretase (ADAM9, ADAM10, TACE/ADAM17) activity and reduces Aβgeneration in vitro. We have generated NRDc transgenic (NRDc-Tg) mice that overexpress NRDc in neuron and NRDc hetero-knockout mice (NRDc+/-). A neuronal overexpression of NRDc in model mice of AD (APP-Tg) led to a decrease in the number and size of amyloid plaques. Analysis of mice which reduces NRDc expression in neuron is still going on. Our findings demonstrate that upregulation of NRDc represents an efficacious therapeutic approach to combating AD in vivo.
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[Journal Article] Nardilysin Regulates Axonal Maturation and Myelination in the Central and Peripheral Nervous System.Nat.2009
Author(s)
Ohno M, Hiraoka Y, Matsuoka T, Tomimoto H, Takao K, Miyakawa T, Oshima N, Kiyonari H, Kimura T, Kita T, Nishi E.
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Journal Title
Neurosci. 12
Pages: 1506-1513
Peer Reviewed
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