2012 Fiscal Year Final Research Report
Deciphering changes in intracellular signals during axon degeneration
| Project/Area Number |
23650184
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIWARA Takeshi 大阪大学, 医学(系)研究科(研究院), 特任准教授(常勤) (50546786)
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| Co-Investigator(Renkei-kenkyūsha) |
MORIMOTO Morimoto 大阪大学, 大学院・医学系研究科, 特任研究員(常勤) (00599996)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 分子神経病理学 / 軸索変性 |
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| Research Abstract |
In this study, our specific aim is to decipher mechanisms and factors that regulate the process of axon degeneration, a hallmark phenotype observed in various neurological disorders including Alzheimer’s disease. We developed aglutamate excitotoxicity-induced axon degeneration system in primary neuronal culturesand found that p150Glued and dynein intermediate chain (DIC), both of which are major components of the retrograde transport dynein-dynactin complex, microtubule stabilization, and inhibition of p53 transactivation regulate the process of axondegeneration including axon degeneration. As glutamate excitotoxicity is implicated in various neurological deficits, our findings identify retrograde transport proteins,microtubule dynamics, and tumor suppressor protein p53 as novel intracellular signalingmodulators of axon degeneration observed in neurological disorders.
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