2007 Fiscal Year Final Research Report Summary
INVESTIGATION OF THE SYNERGIC EFFECT OF β-SYNUCLEIN WITH HSP27 ON NEUROPROTECTION
| Project/Area Number |
17300115
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
HASHIMOTO Makoto Tokyo Metropolitan Organization for Medical Research, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH,TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, LAB DIRECTOR (50189502)
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| Co-Investigator(Kenkyū-buntansha) |
OKADO Haruo TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, LAB DIRECTOR (60221842)
FUJITA Masayo TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, ASSISTANT PROJECT SCIENTIST (90415539)
WEI Jianshe TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, POST DOCTORAL FELLOW (50399466)
NAKAI Masaaki TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, POST DOCTORAL FELLOW (00217647)
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| Project Period (FY) |
2005 – 2007
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| Keywords | SYNUCLEINOPATHY / NEURODEGENERRATION / GENE MUTATION / α-SYNUCLEIN / β-SYNUCLEIN / LYSOSOME / TRANSGENIC MICE / BASAL GANGLIA |
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| Research Abstract |
TWO MISSENSE MUTATIONS (P123H AND V70M) OF BETA-SYNUCLEIN, THE HOMOLOGUE OF ALPHA-SYNUCLEIN, HAVE BEEN RECENTLY IDENTIFIED IN DEMENTIA WITH LEWY BODIES, HOWEVER, THE MECHANISM THROUGH WHICH THESE MUTATIONS INFLUENCE THE PATHOGENESIS OF DEMENTIA WITH LEWY BODIES IS UNCLEAR, TO INVESTIGATE THE ROLE OF THE BETA-SYNUCLEIN MUTATIONS IN NEURODEGENERATION, EACH MUTANT WAS STABLY TRANSFECTED INTO B103 NEUROBLASTOMA CELLS CELLS OVEREXPRESSING MUTATED BETA-SYNUCLEIN HAD ENHANCED LYSOSOMAL, ACTIVITY AND LYSOSOMAL INCLUSION BODIES IN THE CYTOPLASM, SUGGESTING THAT THESE MISSENSE MUTATIONS OF BETA_SYNUCLEIN MIGHT PLAY A CAUSATIVE ROLE IN STIMULATING NEURODEGENETION. SUBSEQUENTLY, WE CREATED TRANSGENIC MICE OVEREXPRESSING P123H BETA-SYNUCLEIN USING THY-1 PROMOTER. THE MICE EXHIBITED AXONAL DEGENERATION AND SYNAPTIC TERMINAL SWELLING, ASSOCIATED WITH PROTEIN AGGREGATION AND BEHAVIOURAL ABNORMALITIES, INCLUDING MOTER DYSFUNCTION. THUS, THESE TRANSGENIC MICE MAY BE USEFUL AS NEW SYNUCLEINOPATHY MODEL MICE. FURTHER STUDY IS IN PROGRESS, INCLUDING CREATION OF BIGENIC MICE BETWEEN P123H BETA-SYNUCLEIN TRANSGENIC MICE AND ALPHA-SYNUCLEIN TRANSGENIC MICE.
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