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NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models
Yang, Chuanbin1; Cai, Cui-Zan2; Song, Ju-Xian1; Tan, Jie-Qiong3; Durairajan, Siva Sundara Kumar1; Iyaswamy, Ashok1; Wu, Ming-Yue2; Chen, Lei-Lei1; Yue, Zhenyu4; Li, Min1; Lu, Jia-Hong2
Source PublicationAUTOPHAGY

Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (A beta) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models. We found that NRBF2 interacts with APP in vivo and its expression levels are reduced in hippocampus of 5XFAD AD mice; we further demonstrated that NRBF2 overexpression promotes degradation of APP C-terminal fragments (APP-CTFs), and reduces A beta(1-40) and A beta(1-42) levels in human mutant APP-overexpressing cells. Conversely, APP-CTFs, A beta 1-40 and A beta 1-42 levels were increased in Nrbf2 knockdown or nrbf2 knockout cells. Furthermore, NRBF2 positively regulates autophagy in neuronal cells and NRBF2-mediated reduction of APP-CTFs levels is autophagy dependent. Importantly, nrbf2 knockout attenuates the recruitment of APP and APP-CTFs into phagophores and the sorting of APP and APP-CTFs into endosomal intralumenal vesicles, which is accompanied by the accumulation of the APP and APP-CTFs into RAB5-positive early endosomes. Collectively, our results reveal the potential connection between NRBF2 and the AD-associated protein APP by showing that NRBF2 plays an important role in regulating degradation of APP-CTFs through modulating autophagy.

Keyworda Beta Alzheimer's Disease App Autophagy Class Iii Phosphatidylinositol 3-kinase (Ptdins3k) Nrbf2
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Indexed BySCI
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000423215800003
The Source to ArticleWOS
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Cited Times [WOS]:25   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
3.State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha, Hunan, China
4.Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Recommended Citation
GB/T 7714
Yang, Chuanbin,Cai, Cui-Zan,Song, Ju-Xian,et al. NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models[J]. AUTOPHAGY,2017,13(12):2028-2040.
APA Yang, Chuanbin.,Cai, Cui-Zan.,Song, Ju-Xian.,Tan, Jie-Qiong.,Durairajan, Siva Sundara Kumar.,...&Lu, Jia-Hong.(2017).NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models.AUTOPHAGY,13(12),2028-2040.
MLA Yang, Chuanbin,et al."NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models".AUTOPHAGY 13.12(2017):2028-2040.
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