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Title: Fibronectin type III domain-containing protein 5 interacts with APP and decreases amyloid β production in Alzheimer's disease
Authors: Noda, Yasuha
Kuzuya, Akira  kyouindb  KAKEN_id
Tanigawa, Kyousuke
Araki, Mitsugu
Kawai, Ryoko
Ma, Biao
Sasakura, Yoko
Maesako, Masato
Tashiro, Yoshitaka
Miyamoto, Masakazu  kyouindb  KAKEN_id
Uemura, Kengo
Okuno, Yasushi  kyouindb  KAKEN_id
Kinoshita, Ayae  kyouindb  KAKEN_id
Author's alias: 宮本, 将和
植村, 健吾
奥野, 恭史
木下, 彩栄
Keywords: Fibronectin Type III Domain-containing Protein 5 (FNDC5)
Amyloid Precursor Protein (APP)
Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA)
HEK293 Cells
Issue Date: 2018
Publisher: Springer Nature
Journal title: Molecular brain
Volume: 11
Thesis number: 61
Abstract: The deposition of Amyloid-beta peptides (Aβ) is detected at an earlier stage in Alzheimer’s disease (AD) pathology. Thus, the approach toward Aβ metabolism is considered to play a critical role in the onset and progression of AD. Mounting evidence suggests that lifestyle-related diseases are closely associated with AD, and exercise is especially linked to the prevention and the delayed progression of AD. We previously showed that exercise is more effective than diet control against Aβ pathology and cognitive deficit in AD mice fed a high-fat diet; however, the underlying molecular mechanisms remain poorly understood. On the other hand, a report suggested that exercise induced expression of fibronectin type III domain-containing protein 5 (FNDC5) in the hippocampus of mice through PGC1α pathway. Thus, in the current study, we investigated a possibility that FNDC5 interacts with amyloid precursor protein (APP) and affects Aβ metabolism. As a result, for the first time ever, we found the interaction between FNDC5 and APP, and forced expression of FNDC5 significantly decreased levels of both Aβ40 and Aβ42 secreted in the media. Taken together, our results indicate that FNDC5 significantly affects β-cleavage of APP via the interaction with APP, finally regulating Aβ levels. A deeper understanding of the mechanisms by which the interaction between APP and FNDC5 may affect Aβ production in an exercise-dependent manner would provide new preventive strategies against the development of AD.
Rights: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
DOI(Published Version): 10.1186/s13041-018-0401-8
PubMed ID: 30355327
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