2003 Fiscal Year Final Research Report Summary
Molecular mechanism of mutant protein degradation in polyglutamine disease
| Project/Area Number |
14580724
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
YAMADA Mitsunori NIIGATA UNIVERSITY, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (30240039)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hitoshi NIIGATA UNIVERSITY, Brain Research Institute, Professor, 脳研究所, 教授 (90206839)
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| Project Period (FY) |
2002 – 2003
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| Keywords | polyglutamine / mouse / olivary hypertrophy / gene expression / pathology |
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| Research Abstract |
Intranuclear accumulation of mutant proteins with expanded polyglutamine(polyQ) tracts is a common pathologic change in neurons of polyglutamine diseases. In dentatorubral-pallidoluysian atrophy(DRPLA) and Machado-Joseph disease, the nuclear pathology occurs in a wide range of CNS regions far beyond the lesion distribution previously established by neuronal loss. This novel pathology may become a clue for elucidating molecular mechanisms of neuronal dysfunction and establishing clinicopathological correlations in polyQ diseases. In addition to the nuclear pathology, we also disclosed the involvement of lysosomal system in the pathogenesis of the diseases. The discovery of polyQ disappearance in hypertrophic olivary neurons in human DRPLA brains enforced us to investigate gene expression profile mediated by the olivary reaction in mice. Oligonucleotide microarray pro filing disclosed the increased levels of several mRNAs encoding protein degradation enzymes.
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Research Products
(12 results)
