| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Research Abstract |
Major cause of Alzheimer's disease is production of β-amyloid (Aβ) and neurotoxic oligomer formation of Aβ. Aβ is a metabolic product generated by cleavage of the amyloid β-protein precursor (APP) by the successive action of β- and γ-secretases. Mutation in the presenilin component of γ-secretase can cause alternative intramembrane processing of APP, leading to aberrant speciation of Aβ, which, in turn, can lead to familial AD (FAD). In contrast to FAD, the primary cause of sporadic type of AD remains unclear. Several membrane and trnasmembrane proteins have been associated with AD, and the disruption of the vesicular transport system is observed in AD brains, suggesting that defects in the membrane trafficking system, including axonal vesicular transport, may be a primitive cause of AD pathogenesis. I focused this research on the analysis of APP vesicular trafficking. APP is known to cargo-receptor of kinesin-1. Our previous studies revealed that APP is associated to KLC through JIP1 mediation. Furthermore, disruption of APP vesicular transprort increased the generation of neurotoxic Aβ. However, the molecular mechanism how APP and kinesin-1 association is regulated remains unclear in detail. We revealed the association between JIP1 and KLC in detail and proposed how the association is regulated.
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