2012 Fiscal Year Final Research Report
Molecular mechanism of apomorphine therapy for Alzheimer disease
| Project/Area Number |
23890150
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
HIMENO Eri 九州大学, 医学研究院, 共同研究員 (10608508)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 神経分子病態学 |
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| Research Abstract |
Alzheimer’s disease (AD) is the major cause of senile dementia, and development of curative drugs is an important issue. We have found apomorphine (APO) to be a novel drug that targets amyloid-β42 (Aβ42) accumulating early in the neurons. In the present research, we revealed 1) that the anti-AD effects of APO is not simply due to stimulation of dopamine receptors; 2) that APO elevates the activity of Insulin-degrading enzyme (IDE) in the cultured cells; 3) that one of the molecular mechanisms of APO effects may be inhibition of the insulin resistance and elevation of the IDE activity; 4) that APO treatment is more effective for the AD mouse model (3xTg-AD) than lithium treatment which inhibits hyper-phosphrylation of tau protein; and 5) that Apokyn(R), a drug of APO for Parkinson’s disease patients, is effective enough at low dose for memory function of the AD mouse model. While, we studied the nature of intracellular Aβ, and have demonstrated that toxic turn Aβ42 accumulates in neurons before onset of memory dysfunction inducing endoplasmic reticulum stress in 3xTg-AD mice.
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[Journal Article] Intracellular accumulation of toxic turn amyloid-β is associated with endoplasmic reticulum stress in Alzheimer's disease2013
Author(s)
Soejima N, Ohyagi Y, Nakamura N, Himeno E, Iinuma KM, Sakae N, Yamasaki R, Tabira T, Murakami K, Irie K, Kinoshita N, LaFerla FM, Kiyohara Y, Iwaki T, Kira J
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Journal Title
Curr Alzheimer Res
Volume: 10
Pages: 11-20
DOI
Peer Reviewed
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[Journal Article] Apomorphine treat-ment in Alzheimer mice promoting amyloid-β degradation2011
Author(s)
Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Yamasaki R, Hashimoto T, Tabira T, LaFerla FM, Kira J
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Journal Title
Ann Neurol
Volume: 69
Pages: 248-256
DOI
Peer Reviewed
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[Journal Article] Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine2011
Author(s)
Ma L, Ohyagi Y, Nakamura N, Iinuma KM, Miyoshi K, Himeno E, Soejima N,Yanagihara YT, Sakae N, Yamasaki R, Kira J
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Journal Title
J Alzheimers Dis
Volume: 27
Pages: 225-237
DOI
Peer Reviewed
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