2011 Fiscal Year Final Research Report
Identification of key uric acid synthesis regulator in novel Parkinson's disease model
| Project/Area Number |
22710195
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical genome science
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 疾患関連遺伝子 / パーキンソン病 / 尿酸代謝分子ネットワーク |
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| Research Abstract |
Parkinson's diseases(PD) is a common neurodegenerative disorder, oxygen radicals and other oxidants attack dopaminergic neuronal cells, causing damage and depletion of dopamine.
Uric acid(UA) is the final product of purine metabolism and plays an important role as a physiological antioxidant(Ames BN Proc. Natl. Acad. Sci. USA 1981). In recent years, several different groups have reported a correlation between decreased UA in PD and clinical progression and stage of PD(Church WH Brain Research Bulletin 1994, Andreadou E Clin. Neurol. Neurosurg. 2009, Weisskopf M. G. Am. J. Epidemiol. 2007, Bogdanov M Brain 2008, Cipriani S Biomark Med. 2010, Johansen KK PLoS One. 2010).
However, little is known about the molecular mechanisms of decreased UA under oxidative stress.
In animal models of PD, oxidative stress has been simulated using parkinsonian neurotoxins that are mitochondrial complex I inhibitors, namely 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP), 6-hydroxy-dopamine(6-OHDA), paraquat(PQ) and totenone(ROT)(Bove J NeuroRx. 2005). PD-associated gene knockout animal models have also been developed(Hatano T J. Neurochem. 2009).
Plasma UA might be expended to resist oxidative injury in PD, but the molecular mechanism of decreased plasma UA in advanced clinical stages of PD has not been analysed in either type of model.
We used our systematic functional annotation pipeline for silkworm genes to identify a novel UA metabolic pathway regulator under oxidative stress in a UA metabolism mutant silkworm Bombyx mori PD model.
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Research Products
(5 results)
