| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Outline of Final Research Achievements |
Endosomal traffic dysfunction in neurons is known as the earliest pathogenic event both in Alzheimer’s disease and Down syndrome. Recent evidence suggests that one of the amyloid-β precursor protein metabolites, beta-carboxyl-terminus fragment (βCTF), accumulates in endosomes and would be responsible for the impairment of endocytic trafficking, but the mechanistic details remain unclear. We identified TMEM30a, a subcomponent of lipid flippase that translocates phospholipids from the outer to inner leaflet of the lipid bilayer, as a candidate partner for βCTF toxicity. TMEM30a interacts with βCTF in endosomes, and this complex impaired retrograde trafficking, leading to abnormally enlarged endosomes. We tried to demonstrate that the complex formation between TMEM30a and βCTF would be involved in the endosomal traffic dysfunction in Down syndrome iPSC-derived neurons and an organotypic hippocampal slice culture model of Alzheimer’s disease.
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