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| 001 | 136120 | ||
| 005 | 20240619104734.0 | ||
| 024 | 7 | _ | |a 10.1038/emboj.2010.167 |2 doi |
| 024 | 7 | _ | |a pmid:20676056 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC2944055 |2 pmc |
| 024 | 7 | _ | |a 0261-4189 |2 ISSN |
| 024 | 7 | _ | |a 1460-2075 |2 ISSN |
| 024 | 7 | _ | |a altmetric:21673495 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-02442 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Kuhn, Peer-Hendrik |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. |
| 260 | _ | _ | |a Hoboken, NJ [u.a.] |c 2010 |b Wiley |
| 264 | _ | 1 | |3 online |2 Crossref |b Wiley |c 2010-07-30 |
| 264 | _ | 1 | |3 print |2 Crossref |b Wiley |c 2010-09-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1718786813_8364 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The 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. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2015-09-01 |2 Crossref |u http://doi.wiley.com/10.1002/tdm_license_1.1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Amyloid beta-Protein Precursor |2 NLM Chemicals |
| 650 | _ | 7 | |a Aplp1 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Membrane Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid Precursor Protein Secretases |0 EC 3.4.- |2 NLM Chemicals |
| 650 | _ | 7 | |a ADAM Proteins |0 EC 3.4.24.- |2 NLM Chemicals |
| 650 | _ | 7 | |a ADAM10 Protein |0 EC 3.4.24.81 |2 NLM Chemicals |
| 650 | _ | 7 | |a Adam10 protein, mouse |0 EC 3.4.24.81 |2 NLM Chemicals |
| 650 | _ | 2 | |a ADAM Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a ADAM10 Protein |2 MeSH |
| 650 | _ | 2 | |a Amyloid Precursor Protein Secretases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Protein Precursor: metabolism |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Cell Line |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mass Spectrometry |2 MeSH |
| 650 | _ | 2 | |a Membrane Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Neurons: enzymology |2 MeSH |
| 650 | _ | 2 | |a Neurons: metabolism |2 MeSH |
| 700 | 1 | _ | |a Wang, Huanhuan |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Dislich, Bastian |0 P:(DE-2719)9000408 |b 2 |
| 700 | 1 | _ | |a Colombo, Alessio |0 P:(DE-2719)2340744 |b 3 |
| 700 | 1 | _ | |a Zeitschel, Ulrike |b 4 |
| 700 | 1 | _ | |a Ellwart, Joachim W |b 5 |
| 700 | 1 | _ | |a Kremmer, Elisabeth |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Rossner, Steffen |b 7 |
| 700 | 1 | _ | |a Lichtenthaler, Stefan |0 P:(DE-2719)2181459 |b 8 |e Last author |
| 773 | 1 | 8 | |a 10.1038/emboj.2010.167 |b : Wiley, 2010-07-30 |n 17 |p 3020-3032 |3 journal-article |2 Crossref |t The EMBO Journal |v 29 |y 2010 |x 0261-4189 |
| 773 | _ | _ | |a 10.1038/emboj.2010.167 |g Vol. 29, no. 17, p. 3020 - 3032 |0 PERI:(DE-600)1467419-1 |n 17 |q 29:17<3020 - 3032 |p 3020-3032 |t The EMBO journal |v 29 |y 2010 |x 0261-4189 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944055 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/136120/files/DZNE-2020-02442_Restricted.pdf |
| 856 | 4 | _ | |u https://pub.dzne.de/record/136120/files/DZNE-2020-02442_Restricted.pdf?subformat=pdfa |x pdfa |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 2 |6 P:(DE-2719)9000408 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 3 |6 P:(DE-2719)2340744 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 8 |6 P:(DE-2719)2181459 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |3 G:(DE-HGF)POF3 |2 G:(DE-HGF)POF3-300 |4 G:(DE-HGF)POF |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2010 |
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| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |
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| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0110 |2 StatID |b Science Citation Index |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0111 |2 StatID |b Science Citation Index Expanded |
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| 920 | 1 | _ | |0 I:(DE-2719)1110006 |k AG Lichtenthaler |l Neuroproteomics |x 0 |
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