140621 20240430120009.0 10.1038/s41420-017-0003-8 doi pmid:29531801 pmid pmc:PMC5841321 pmc altmetric:32357431 altmetric DZNE-2020-06943 English 610 Matthes, Frank P:(DE-2719)2810945 0 First author Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis. London 2018 Nature Publishing Group online Crossref Springer Science and Business Media LLC 2018-01-29 print Crossref Springer Science and Business Media LLC 2018-12-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1714467224_8222 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Alzheimer's disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently Aβ in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 2018-01-29 Crossref http://creativecommons.org/licenses/by/4.0 Dataset connected to CrossRef, PubMed, Hettich, Moritz M P:(DE-2719)2380493 1 Schilling, Judith P:(DE-2719)2810643 2 Flores-Dominguez, Diana P:(DE-2719)9000076 3 Blank, Nelli P:(DE-2719)2811722 4 Wiglenda, Thomas 5 Buntru, Alexander 6 Wolf, Hanna P:(DE-2719)2630412 7 Weber, Stephanie P:(DE-2719)2662310 8 Vorberg, Ina P:(DE-2719)2481765 9 Dagane, Alina 10 Dittmar, Gunnar 11 Wanker, Erich 12 Ehninger, Dan P:(DE-2719)2289209 13 Krauß, Sybille P:(DE-2719)2421562 14 Last author dzne 10.1038/s41420-017-0003-8 : Springer Science and Business Media LLC, 2018-01-29 1 4 journal-article Crossref Cell Death Discovery 4 2018 2058-7716 10.1038/s41420-017-0003-8 Vol. 4, no. 1, p. 4 PERI:(DE-600)2842546-7 1 4:1<4 4 Cell death discovery 4 2018 2058-7716 OpenAccess http://pub.dzne.de/record/140621/files/DZNE-2020-06943.pdf OpenAccess pdfa http://pub.dzne.de/record/140621/files/DZNE-2020-06943.pdf?subformat=pdfa Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841321 oai:pub.dzne.de:140621 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2810945 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2380493 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2810643 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)9000076 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2811722 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2630412 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2662310 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)2481765 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 13 P:(DE-2719)2289209 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 14 P:(DE-2719)2421562 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 2018 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-03-31 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-03-31 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2023-03-31 JCR StatID:(DE-HGF)0100 StatID CELL DEATH DISCOV : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-03-31 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2023-03-31 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-02-14T16:19:13Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2023-03-31 Fees StatID:(DE-HGF)0700 StatID 2023-03-31 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-03-31 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-02-14T16:19:13Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2023-03-31 IF >= 5 StatID:(DE-HGF)9905 StatID CELL DEATH DISCOV : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-03-31 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-03-31 I:(DE-2719)1011006 AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 0 I:(DE-2719)1013005 AG Ehninger Translational Biogerontology 1 I:(DE-2719)1013004 AG Vorberg Prion Cell Biology 2 journal VDB UNRESTRICTED I:(DE-2719)1011006 I:(DE-2719)1013005 I:(DE-2719)1013004 FullTexts -- missing cx lookup -- 10.1002/ca.980080612 Crossref 10.1002/ca.980080612 -- missing cx lookup -- 10.7326/0003-4819-113-6-429 Crossref 10.7326/0003-4819-113-6-429 -- missing cx lookup -- 10.1192/bjp.157.1.72 Crossref 10.1192/bjp.157.1.72 -- missing cx lookup -- 10.1073/pnas.94.1.298 Crossref 10.1073/pnas.94.1.298 -- missing cx lookup -- 10.1007/s00702-004-0221-0 Crossref 10.1007/s00702-004-0221-0 -- missing cx lookup -- 10.1159/000067425 Crossref 10.1159/000067425 -- missing cx lookup -- 10.1073/pnas.0912793107 Crossref 10.1073/pnas.0912793107 -- missing cx lookup -- 10.1038/ng762 Crossref 10.1038/ng762 -- missing cx lookup -- 10.1073/pnas.1100131108 Crossref 10.1073/pnas.1100131108 -- missing cx lookup -- 10.1101/gad.887201 Crossref 10.1101/gad.887201 -- missing cx lookup -- 10.1074/jbc.M111.224451 Crossref 10.1074/jbc.M111.224451 -- missing cx lookup -- 10.1038/ncomms2514 Crossref 10.1038/ncomms2514 -- missing cx lookup -- 10.1007/s00439-007-0456-6 Crossref 10.1007/s00439-007-0456-6 -- missing cx lookup -- 10.1186/1471-2407-14-52 Crossref 10.1186/1471-2407-14-52 -- missing cx lookup -- 10.1371/journal.pone.0102420 Crossref 10.1371/journal.pone.0102420 -- missing cx lookup -- 10.1186/1476-4598-13-146 Crossref 10.1186/1476-4598-13-146 -- missing cx lookup -- 10.1111/j.1432-1033.1969.tb00629.x Crossref 10.1111/j.1432-1033.1969.tb00629.x -- missing cx lookup -- 10.1016/j.cell.2006.01.016 Crossref 10.1016/j.cell.2006.01.016 -- missing cx lookup -- 10.1042/BST20120080 Crossref 10.1042/BST20120080 -- missing cx lookup -- 10.1074/jbc.M110.100420 Crossref 10.1074/jbc.M110.100420 -- missing cx lookup -- 10.1111/j.1532-5415.2012.03916.x Crossref 10.1111/j.1532-5415.2012.03916.x -- missing cx lookup -- 10.2337/dc13-0229 Crossref 10.2337/dc13-0229 -- missing cx lookup -- 10.1016/j.neuropharm.2011.01.033 Crossref 10.1016/j.neuropharm.2011.01.033 -- missing cx lookup -- 10.1073/pnas.0807991106 Crossref 10.1073/pnas.0807991106 -- missing cx lookup -- 10.1016/j.pbb.2012.03.002 Crossref 10.1016/j.pbb.2012.03.002 -- missing cx lookup -- 10.3233/JAD-141332 Crossref 10.3233/JAD-141332 -- missing cx lookup -- 10.1016/j.bbamcr.2015.01.017 Crossref 10.1016/j.bbamcr.2015.01.017 -- missing cx lookup -- 10.1371/journal.pone.0005088 Crossref 10.1371/journal.pone.0005088 -- missing cx lookup -- 10.1007/s00216-015-8595-4 Crossref 10.1007/s00216-015-8595-4 -- missing cx lookup -- 10.1038/nprot.2007.261 Crossref 10.1038/nprot.2007.261 -- missing cx lookup -- 10.1038/nbt.1511 Crossref 10.1038/nbt.1511 -- missing cx lookup -- 10.1073/pnas.0910723107 Crossref 10.1073/pnas.0910723107 -- missing cx lookup -- 10.1038/nsmb.1437 Crossref 10.1038/nsmb.1437