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| Home > Publications Database > Loss of PAFAH1B2 reduces amyloid-β generation by promoting the degradation of amyloid precursor protein C-terminal fragments. > print |
| 001 | 136732 | ||
| 005 | 20240321220127.0 | ||
| 024 | 7 | _ | |a 10.1523/JNEUROSCI.2681-12.2012 |2 doi |
| 024 | 7 | _ | |a pmid:23238734 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC6621731 |2 pmc |
| 024 | 7 | _ | |a 0270-6474 |2 ISSN |
| 024 | 7 | _ | |a 1529-2401 |2 ISSN |
| 024 | 7 | _ | |a altmetric:1127812 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-03054 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Page, Richard M |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Loss of PAFAH1B2 reduces amyloid-β generation by promoting the degradation of amyloid precursor protein C-terminal fragments. |
| 260 | _ | _ | |a Washington, DC |c 2012 |b Soc.57413 |
| 264 | _ | 1 | |3 online |2 Crossref |b Society for Neuroscience |c 2012-12-12 |
| 264 | _ | 1 | |3 print |2 Crossref |b Society for Neuroscience |c 2012-12-12 |
| 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 1589983267_10886 |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 Amyloid-β peptide (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease. In view of the side effects associated with inhibiting the secretases that produce Aβ, new molecular targets are required to provide alternative therapeutic options. We used RNA interference (RNAi) to systematically screen the Drosophila genome to identify genes that modulate Aβ production upon knockdown. RNAi of 41 genes in Drosophila cells significantly lowered Aβ without affecting general secretion or viability. After the γ-secretase complex components, the most potent effect was observed for platelet activating factor acetylhydrolase α (Paf-AHα), and, in mammalian cells, the effect was replicated for its ortholog PAFAH1B2. Knockdown of PAFAH1B2 strongly reduced Aβ secretion from human cells, and this effect was confirmed in primary cells derived from PAFAH1B2 knock-out mice. Reduced Aβ production was not attributable to altered β-amyloid precursor protein (APP) ectodomain shedding but was a result of an enhanced degradation of APP C-terminal fragments (CTFs) in the absence of PAFAH1B2 but not its close homolog PAFAH1B3. Enhanced degradation of APP CTFs was selective because no such effects were obtained for Notch or E-/N-cadherin. Thus, we have identified an important protein that can selectively modify Aβ generation via a novel mechanism, namely enhanced degradation of its immediate precursor. In view of the absence of a neurological phenotype in PAFAH1B2 knock-out mice, targeted downregulation of PAFAH1B2 may be a promising new strategy for lowering Aβ. |
| 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 2013-06-12 |2 Crossref |u https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Amyloid beta-Peptides |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid beta-Protein Precursor |2 NLM Chemicals |
| 650 | _ | 7 | |a Microtubule-Associated Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Peptide Fragments |2 NLM Chemicals |
| 650 | _ | 7 | |a 1-Alkyl-2-acetylglycerophosphocholine Esterase |0 EC 3.1.1.47 |2 NLM Chemicals |
| 650 | _ | 7 | |a PAFAH1B1 protein, human |0 EC 3.1.1.47 |2 NLM Chemicals |
| 650 | _ | 2 | |a 1-Alkyl-2-acetylglycerophosphocholine Esterase: genetics |2 MeSH |
| 650 | _ | 2 | |a 1-Alkyl-2-acetylglycerophosphocholine Esterase: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Protein Precursor: metabolism |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Drosophila |2 MeSH |
| 650 | _ | 2 | |a Gene Knockdown Techniques |2 MeSH |
| 650 | _ | 2 | |a HEK293 Cells |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Mice, Knockout |2 MeSH |
| 650 | _ | 2 | |a Microtubule-Associated Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Microtubule-Associated Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Peptide Fragments: metabolism |2 MeSH |
| 650 | _ | 2 | |a RNA Interference |2 MeSH |
| 650 | _ | 2 | |a Transfection |2 MeSH |
| 700 | 1 | _ | |a Münch, Anna |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Horn, Thomas |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Kuhn, Peer-Hendrik |0 P:(DE-2719)2810327 |b 3 |
| 700 | 1 | _ | |a Colombo, Alessio |0 P:(DE-2719)2340744 |b 4 |
| 700 | 1 | _ | |a Reiner, Orly |b 5 |
| 700 | 1 | _ | |a Boutros, Michael |b 6 |
| 700 | 1 | _ | |a Steiner, Harald |0 P:(DE-2719)2000023 |b 7 |
| 700 | 1 | _ | |a Lichtenthaler, Stefan F |0 P:(DE-2719)2181459 |b 8 |
| 700 | 1 | _ | |a Haass, Christian |0 P:(DE-2719)2202037 |b 9 |e Last author |
| 773 | 1 | 8 | |a 10.1523/jneurosci.2681-12.2012 |b Society for Neuroscience |d 2012-12-12 |n 50 |p 18204-18214 |3 journal-article |2 Crossref |t The Journal of Neuroscience |v 32 |y 2012 |x 0270-6474 |
| 773 | _ | _ | |a 10.1523/JNEUROSCI.2681-12.2012 |g Vol. 32, no. 50, p. 18204 - 18214 |0 PERI:(DE-600)1475274-8 |n 50 |q 32:50<18204 - 18214 |p 18204-18214 |t The journal of neuroscience |v 32 |y 2012 |x 0270-6474 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621731 |
| 909 | C | O | |p VDB |o oai:pub.dzne.de:136732 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 3 |6 P:(DE-2719)2810327 |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 9 |6 P:(DE-2719)2202037 |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |2 G:(DE-HGF)POF3-300 |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2012 |
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| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |
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| 920 | 1 | _ | |0 I:(DE-2719)1110000-1 |k AG Steiner |l Biochemistry of γ-Secretase |x 1 |
| 920 | 1 | _ | |0 I:(DE-2719)1110007 |k AG Haass old |l ALS, FTLD and Zebrafish models |x 2 |
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