PMID- 28980867
OWN - NLM
STAT- MEDLINE
DCOM- 20190705
LR  - 20201209
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 13
IP  - 12
DP  - 2017
TI  - NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer 
      disease models.
PG  - 2028-2040
LID - 10.1080/15548627.2017.1379633 [doi]
AB  - 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 (Abeta) 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 Abeta(1-40) and Abeta(1-42) levels in human mutant 
      APP-overexpressing cells. Conversely, APP-CTFs, Abeta(1-40) and Abeta(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.
FAU - Yang, Chuanbin
AU  - Yang C
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Cai, Cui-Zan
AU  - Cai CZ
AD  - b State Key Laboratory of Quality Research in Chinese Medicine , Institute of 
      Chinese Medical Sciences , University of Macau , Taipa, Macau SAR , China.
FAU - Song, Ju-Xian
AU  - Song JX
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Tan, Jie-Qiong
AU  - Tan JQ
AD  - c State Key Laboratory of Medical Genetics , Xiangya Medical School , Central 
      South University , Changsha, Hunan , China.
FAU - Durairajan, Siva Sundara Kumar
AU  - Durairajan SSK
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Iyaswamy, Ashok
AU  - Iyaswamy A
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Wu, Ming-Yue
AU  - Wu MY
AD  - b State Key Laboratory of Quality Research in Chinese Medicine , Institute of 
      Chinese Medical Sciences , University of Macau , Taipa, Macau SAR , China.
FAU - Chen, Lei-Lei
AU  - Chen LL
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Yue, Zhenyu
AU  - Yue Z
AD  - d Department of Neurology and Neuroscience , Friedman Brain Institute , Icahn 
      School of Medicine at Mount Sinai , New York , NY , USA.
FAU - Li, Min
AU  - Li M
AD  - a Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research , School of 
      Chinese Medicine , Hong Kong Baptist University , Hong Kong SAR , China.
FAU - Lu, Jia-Hong
AU  - Lu JH
AD  - b State Key Laboratory of Quality Research in Chinese Medicine , Institute of 
      Chinese Medical Sciences , University of Macau , Taipa, Macau SAR , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Nrbf2 protein, mouse)
RN  - 0 (Peptide Fragments)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Alzheimer Disease/*pathology
MH  - Amyloid beta-Peptides/*chemistry/*metabolism
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Proteins
MH  - Disease Models, Animal
MH  - Endosomes/metabolism
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Neurons/metabolism
MH  - Peptide Fragments/*metabolism
MH  - Protein Binding
MH  - *Proteolysis
MH  - Trans-Activators
MH  - Transcription Factors/*metabolism
PMC - PMC5788544
OTO - NOTNLM
OT  - APP
OT  - Alzheimer's disease
OT  - Abeta
OT  - NRBF2
OT  - autophagy
OT  - class III phosphatidylinositol 3-kinase (PtdIns3K)
EDAT- 2017/10/06 06:00
MHDA- 2019/07/06 06:00
PMCR- 2018/10/05
CRDT- 2017/10/06 06:00
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2019/07/06 06:00 [medline]
PHST- 2017/10/06 06:00 [entrez]
PHST- 2018/10/05 00:00 [pmc-release]
AID - 1379633 [pii]
AID - 10.1080/15548627.2017.1379633 [doi]
PST - ppublish
SO  - Autophagy. 2017;13(12):2028-2040. doi: 10.1080/15548627.2017.1379633.