2003 Fiscal Year Final Research Report Summary
Identified the causative gene for EAOH end elucidation the molecular mechanisms of neurodegeneration in EAOH
| Project/Area Number |
14207029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUJI Shoji The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (70150612)
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| Co-Investigator(Kenkyū-buntansha) |
OYAKE Mutsuo Niigata University, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (70313559)
ONODERA Osamu Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (20303167)
GOTO Jun The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (10211252)
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| Project Period (FY) |
2002 – 2003
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| Keywords | spinocerebellar degeneration / DNA repair / single strand DNA break / aprataxin / ocular motor apraxia / liypoalbuminemia / cerebellum / 小脳 |
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| Research Abstract |
We have previously identified the causative gene for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), an autosomal recessive neurodegenerative disease. We named the causative gene "aprataxin". This study was aimed to elucidate the molecular mechanisms of neurodegeneration in EAOH and, furthermore, to establish the therapeutic strategies for this diseases. In previous studies we showed that there are two major isoforms of aprataxin mRNA, of which we demonstrated that long form aprataxin is the component essential for its physiological function. Furthermore, we identified that aprataxin interacts with XRCC1 (X-ray repair cross complementing group 1) based on yeast two hybrid assay as well as im nuno coprecipitation experiments, raising the possibility that aprataxin has a physiological function in single strand DNA break repair (SSBR). In vitro reconstitution experiments of SSBR demonstrated that aprataxin contains 5'-phophatase as well as 3'-phophatase activities.Taken together these findings suggest that aprataxin is a new member of molecules involved in SSBR.
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