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000136120 041__ $$aEnglish
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000136120 1001_ $$0P:(DE-HGF)0$$aKuhn, Peer-Hendrik$$b0
000136120 245__ $$aADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons.
000136120 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2010
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000136120 520__ $$aThe amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called alpha-secretase. This is considered an important mechanism preventing the generation of the Alzheimer's disease amyloid-beta peptide (Abeta). alpha-Secretase appears to be a metalloprotease of the ADAM family, but its identity remains to be established. Using a novel alpha-secretase-cleavage site-specific antibody, we found that RNAi-mediated knockdown of ADAM10, but surprisingly not of ADAM9 or 17, completely suppressed APP alpha-secretase cleavage in different cell lines and in primary murine neurons. Other proteases were not able to compensate for this loss of alpha-cleavage. This finding was further confirmed by mass-spectrometric detection of APP-cleavage fragments. Surprisingly, in different cell lines, the reduction of alpha-secretase cleavage was not paralleled by a corresponding increase in the Abeta-generating beta-secretase cleavage, revealing that both proteases do not always compete for APP as a substrate. Instead, our data suggest a novel pathway for APP processing, in which ADAM10 can partially compete with gamma-secretase for the cleavage of a C-terminal APP fragment generated by beta-secretase. We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.
000136120 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000136120 542__ $$2Crossref$$i2015-09-01$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1
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000136120 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000136120 650_7 $$2NLM Chemicals$$aAplp1 protein, mouse
000136120 650_7 $$2NLM Chemicals$$aMembrane Proteins
000136120 650_7 $$0EC 3.4.-$$2NLM Chemicals$$aAmyloid Precursor Protein Secretases
000136120 650_7 $$0EC 3.4.24.-$$2NLM Chemicals$$aADAM Proteins
000136120 650_7 $$0EC 3.4.24.81$$2NLM Chemicals$$aADAM10 Protein
000136120 650_7 $$0EC 3.4.24.81$$2NLM Chemicals$$aAdam10 protein, mouse
000136120 650_2 $$2MeSH$$aADAM Proteins: metabolism
000136120 650_2 $$2MeSH$$aADAM10 Protein
000136120 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: metabolism
000136120 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000136120 650_2 $$2MeSH$$aAnimals
000136120 650_2 $$2MeSH$$aCell Line
000136120 650_2 $$2MeSH$$aHumans
000136120 650_2 $$2MeSH$$aMass Spectrometry
000136120 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000136120 650_2 $$2MeSH$$aMice
000136120 650_2 $$2MeSH$$aNeurons: enzymology
000136120 650_2 $$2MeSH$$aNeurons: metabolism
000136120 7001_ $$0P:(DE-HGF)0$$aWang, Huanhuan$$b1
000136120 7001_ $$0P:(DE-2719)9000408$$aDislich, Bastian$$b2
000136120 7001_ $$0P:(DE-2719)2340744$$aColombo, Alessio$$b3
000136120 7001_ $$aZeitschel, Ulrike$$b4
000136120 7001_ $$aEllwart, Joachim W$$b5
000136120 7001_ $$0P:(DE-HGF)0$$aKremmer, Elisabeth$$b6
000136120 7001_ $$aRossner, Steffen$$b7
000136120 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan$$b8$$eLast author
000136120 77318 $$2Crossref$$3journal-article$$a10.1038/emboj.2010.167$$b : Wiley, 2010-07-30$$n17$$p3020-3032$$tThe EMBO Journal$$v29$$x0261-4189$$y2010
000136120 773__ $$0PERI:(DE-600)1467419-1$$a10.1038/emboj.2010.167$$gVol. 29, no. 17, p. 3020 - 3032$$n17$$p3020-3032$$q29:17<3020 - 3032$$tThe EMBO journal$$v29$$x0261-4189$$y2010
000136120 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944055
000136120 8564_ $$uhttps://pub.dzne.de/record/136120/files/DZNE-2020-02442_Restricted.pdf
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