| Project/Area Number |
23300128
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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 | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NUKINA Nobuyuki 順天堂大学, 医学研究科, 客員教授 (10134595)
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| Co-Investigator(Renkei-kenkyūsha) |
MURAYAMA Takashi 順天堂大学, 医学部, 准教授 (10230012)
KASHIYAMA Taku 順天堂大学, 医学部, 助教 (90338343)
ARAYA Runa 順天堂大学, 医学部, 助教 (10391848)
KAMIKUBO Yuji 順天堂大学, 医学部, 助教 (80509670)
TAKASUGI Nobumasa 順天堂大学, 医学部, 助教 (60436590)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 脳神経疾患 / 認知症 / 脂質 / アルツハイマー病 / 痴呆 |
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| Outline of Final Research Achievements |
Aggregation and deposition of amyloid β peptide (Aβ) in the brain is considered central to the pathogenesis of Alzheimer’s disease (AD). Aβ is produced through a sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Increasing evidence indicates that membrane microdomains play an important role as a platform for the vesicular transport of APP in the secretory and endocytic pathways and in the amyloidogenic processing of APP. Recently, accumulation of β-secretase-cleaved C-terminal fragment of APP (βCTF), which is the direct precursor of Aβ, was found to cause endosome dysfunction during the early phase of AD that could drive Aβ overproduction. To gain insight into the underlying molecular mechanisms, we examined the functions of endosomal proteins in the APP-containing microdomains. We identified a candidate protein that causes impairment of endocytic membrane traffic through its interactions with βCTF.
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