Neuroprotective factor, Colibelin, against ALS related insults : Characterization by circular Dichroism and sedimentation equilibrium
Project/Area Number |
17590893
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Keio University |
Principal Investigator |
KITA Yoshiko Keio University, School of Medicine, Assistant professor (00327496)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Amyotrophic lateral screlosis / Alzheimer's disease / ADNF / HN(Humanin) / Colivelin / G93A-SOD 1 / MND / Neurodeeenerative disease / ALS |
Research Abstract |
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, characterized by progressive systemic loss of motor neurons. There is no sufficiently effective therapy for ALS. We have previously reported that intracerebroventicular injection of ADNF, a glia-derived neurotrophic peptide, improves motor performance of G93A-SOD 1 transgenic mice. In this study, we found that Colivelin, hybrid peptide of ADNF and a most potent Humanin derivative, AGAC8R-BNG17, exerts its neuroprotection against both ALS and Alzheimer's disease (AD) related insults at around 100 fM. Colivelin prolongs survival of an ALS model mice though ADNF could not. We further found that Colivelin was able to suppress impairment in spatial working memory induced by intracerebroventicular injection of Abeta 25.35-or Abeta 42. In order to investigate the femtomolar acting neuroprotection of Colivelin, we have been characterizing the component peptides ADNF and AGAC8R-HNG17 as well as Colivelin by circular dic
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hroism (CD) and sedimentation equilibrium. ADNF was a monomer in solution over the wide range of its concentration suggesting that it exerts neuroprotection with monomer form in physiological condition. The sedimentation equilibrium experiments demonstrated monomeric structure of Colivelinl as well. It was suggested by CD analysis that Colivelin was a completely different molecule from simple mixture molecules of ADNF and AGAC8R-HNG17. The structure of a highly potent HNG was examined by CD. The secondary structure is more disordered in water than in PBS. The peptide structure in water is little dependent on both peptide concentration and temperature. On the contrary, the peptide structure was significantly different in PBS from the structure in water. The observed different structure in PBS appears to be due to self-association of the peptide via hydrophobic interaction. The wild-type Humanin also behaved similarly, i.e., it assumed a disordered structure in water but underwent conformational changes in PBS. Less
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Report
(3 results)
Research Products
(35 results)
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[Journal Article] Expression of N19S-SOD1,a SOD1 mutant found in sporadic Amyotrophic lateral sclerosis(ALS)patients,induces low-grade motoneuronal toxicity2005
Author(s)
Obata Y, Niikura T, Kanekura K, Hashimoto Y, Kawasumi M, Kita Y, Aiso S, Matsuoka M, Nishimoto I.
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Journal Title
J.Neurosci.Res. 81
Pages: 720-729
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Expression of N19S-SOD1, a SOD1 mutant found in sporadic amyotrophic lateral sclerosis(ALS)'Patients, induces low-grade motoneuronal toxicity2005
Author(s)
Obata Y, Niikura T, Kanekura K, Hashimoto Y, Kawasumi M, Rita Y, Aiso S, Matsuoka M, Nishimoto I.
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Journal Title
J. Neurosci. Res. 81
Pages: 720-29
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Implanted cannula-mediated repetitive administration of Abeta 25-35 into the mouse cerebral venticle effectively impairs spatial working2005
Author(s)
Yamada M, Chiba T, Sasabe J, Nawa M, Tajima H, Niikura T, Terashita K, Aiso S, Kita Y, Matsuoka M, Nishimoto I
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Journal Title
Behav Brain Res. 164
Pages: 139-146
Related Report
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[Journal Article] A Humanin derivative, S14G-HN, prevents amyloid-b-induced memory impairment in mice2005
Author(s)
Tajima H, Kawasumi M, Chiba T, Yamada M, Yamashita K, Nawa M, Kita Y, Kouyama K, Aiso S, Matsuoka M, Niikura T, Nishimoto I
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Journal Title
J.Neurosci.Res. 79
Pages: 714-723
Related Report
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[Journal Article] Expression of N19S-SOD1, a SOD1 mutant found in sporadic amyotrophic lateral sclerosis (ALS) patients, induces low-grade motoneuronal toxicity2005
Author(s)
Obata Y, Niikura T, Kanekura K, Hashimoto Y, Kawasumi M, Kita Y, Aiso S, Matsuoka M, Nishimoto I
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Journal Title
J.Neurosci.Res. 81
Pages: 720-729
Related Report
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