title: c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration.
abstract: Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD. [BMB Reports 2016; 49(7): 376-381].
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Sang-Pil
authors.initials: SP
authors.lastname: So
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center, University of Ulsan College of Medicine; Department of Brain Science, University of Ulsan College of Medicine; Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Dong-Hou
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D000873:Anthracenes; C432165:pyrazolanthrone; D019319:Okadaic Acid; D048031:JNK Mitogen-Activated Protein Kinases
references.citation: J Biol Chem. 2003 Jun 20;278(25):22946-55
references.pmid: 12665528
references.citation: Science. 1997 Aug 1;277(5326):693-6
references.pmid: 9235893
references.citation: J Neurochem. 2000 Sep;75(3):1085-91
references.pmid: 10936190
references.citation: Mol Neurodegener. 2014 Jan 11;9:6
references.pmid: 24410826
references.citation: Neurotoxicology. 2013 Jul;37:163-72
references.pmid: 23688530
references.citation: Science. 2002 Jul 19;297(5580):353-6
references.pmid: 12130773
references.citation: J Cell Biol. 2003 Oct 13;163(1):83-95
references.pmid: 14557249
references.citation: BMB Rep. 2016 Jun;49(6):337-42
references.pmid: 26779997
references.citation: Aging Cell. 2015 Oct;14(5):878-86
references.pmid: 26178297
references.citation: Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
references.pmid: 3088567
references.citation: Neurosci Lett. 2006 Feb 20;394(3):190-5
references.pmid: 16260088
references.citation: Nature. 2006 Mar 23;440(7083):528-34
references.pmid: 16554819
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98 (24):13681-6
references.pmid: 11717429
references.citation: Curr Alzheimer Res. 2012 Feb;9(2):217-26
references.pmid: 21605029
references.citation: FEBS Lett. 2003 Jul 17;547(1-3):193-6
references.pmid: 12860412
references.citation: J Biol Chem. 2008 Oct 31;283(44):29633-7
references.pmid: 18650433
references.citation: Am J Pathol. 2005 Jun;166(6):1761-71
references.pmid: 15920161
references.citation: Ann Neurol. 2014 Jan;75(1):88-97
references.pmid: 24114864
references.citation: J Neurosci. 2007 Feb 21;27(8):1981-91
references.pmid: 17314294
references.citation: Biochem Biophys Res Commun. 2007 Jun 15;357(4):1004-10
references.pmid: 17459339
references.citation: Biochem Soc Trans. 2006 Nov;34(Pt 5):828-32
references.pmid: 17052208
references.citation: Neuroscience. 2003;118(4):1175-82
references.pmid: 12732260
references.citation: J Neurosci. 2005 Apr 13;25(15):3741-51
references.pmid: 15829626
references.citation: PLoS One. 2006 Dec 20;1:e51
references.pmid: 17183681
references.citation: J Neurochem. 1993 Aug;61(2):673-82
references.pmid: 8336148
references.citation: Nature. 1987 Feb 19-25;325(6106):733-6
references.pmid: 2881207
references.citation: Neurobiol Dis. 2006 May;22(2):435-44
references.pmid: 16480887
references.citation: J Biol Chem. 2009 Dec 11;284(50):34628-39
references.pmid: 19801628
references.citation: Ann Neurol. 1997 Jan;41(1):17-24
references.pmid: 9005861
references.citation: BMB Rep. 2015 Jun;48(6):324-9
references.pmid: 25047444