2005 Fiscal Year Final Research Report Summary
Formation of ion chyannels by amyloidogenic proteins and screening for protective substances
| Project/Area Number |
14572106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | School of Pharmaceutical Sciences, Kyushu University of Health and Welfare (2003-2005)
Tokyo Metropolitan Organization for Medical Research (2002) |
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Principal Investigator |
KAWAHARA Masahiro School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Prof., 薬学部, 教授 (40224828)
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| Co-Investigator(Kenkyū-buntansha) |
KONOHA Keiko School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Res.Assist, 薬学部, 助手 (00369175)
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| Project Period (FY) |
2002 – 2005
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| Keywords | calcium homeostasis / prion disease / Alzheimer's disease / copper / zinc / apoptosis / cell culture / membrane lipid |
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| Research Abstract |
The conformational changes of Alzheimer's β-amyloid protein (AβP) enhance its neurotoxicity, and finally lead to Alzheimer's pathogenesis. Recent studies have suggested that a common mechanism is based on the diverse diseases termed "conformational diseases" including other neurodegenerative diseases such as prion diseases, Parkinson's disease, and Huntington's disease. These diseases share similarity in the formation of β-sheet containing amyloid fibrils by disease-related proteins such including prion protein, a-synuclein, polyglutamine and the introduction of apoptotic degeneration. Although the molecular mechanism of neurodegeneration induced by these conformational disease-related proteins remains elusive, these proteins have the ability to directly incorporate into membranes and to form calcium-permeable ion channels. In this research, we have investigated the detailed characteristics of channel formation by amyloidogenic proteins including beta-amyloid protein, prion protein fragment peptides, alpha-synuclein fragment peptides using Ca imaging system. We found that these proteins cause rapid increase of intracellular Ca levels. Amyloid peptides composed by D-amino acid residues also cause similar Ca increase. No known transmitter inhibitors or channel blockers inhibit the Ca changes. Therefore, we conclude that Ca increase caused by these amyloidogenic peptides are based on the "amyloid channels". Furthermore, we searched substances which prevent Ca increase induced by amyloid proteins for the aim of screening possible treatment for theses neurodegenerative diseases. Several neurosteroids marked inhibit the Ca increase. Moreover, we investigated the effects of trace metals which effect the conformational changes of amyloidogenic proteins.
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Research Products
(37 results)
