{"doi":"10.1038/emboj.2010.167","title":"ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons","abstract":null,"journal":"The EMBO Journal","year":2010,"id":591488,"datarank":9.51561902203004,"base_score":6.405228458030842,"endowment":6.405228458030842,"self_citation_contribution":0.9607842687046264,"citation_network_contribution":8.554834753325412,"self_endowment_contribution":0.9607842687046264,"citer_contribution":8.554834753325412,"corpus_percentile":null,"corpus_rank":null,"citation_count":604,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1259303,"name":"Huanhuan Wang","orcid":"0000-0003-0452-9588","position":1,"is_corresponding":false},{"id":1325965,"name":"Bastian Dislich","orcid":"0000-0002-4838-4686","position":2,"is_corresponding":false},{"id":1513367,"name":"Alessio Colombo","orcid":null,"position":3,"is_corresponding":false},{"id":1513368,"name":"Ulrike Zeitschel","orcid":null,"position":4,"is_corresponding":false},{"id":1513369,"name":"Joachim W Ellwart","orcid":null,"position":5,"is_corresponding":false},{"id":116900,"name":"Elisabeth Kremmer","orcid":null,"position":6,"is_corresponding":false},{"id":1065841,"name":"Steffen Roßner","orcid":"0000-0002-9959-283X","position":7,"is_corresponding":false},{"id":1513370,"name":"Stefan F Lichtenthaler","orcid":null,"position":8,"is_corresponding":false},{"id":336980,"name":"Peer‐Hendrik Kuhn","orcid":"0000-0001-7891-5102","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons","abstract":"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.","is_dataset_classified":null,"base_score":6.405228458030842,"endowment":6.405228458030842,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20676056","pmcid":"PMC2944055","openalex_id":"https://openalex.org/W2137592631","authors":[],"funders":[],"total_grants":0,"fwci":22.6821,"citation_percentile":0.9979972,"influential_citations":0,"citation_trend":[{"year":2012,"count":48},{"year":2013,"count":44},{"year":2014,"count":41},{"year":2015,"count":42},{"year":2016,"count":42},{"year":2017,"count":40},{"year":2018,"count":43},{"year":2019,"count":44},{"year":2020,"count":41},{"year":2021,"count":40},{"year":2022,"count":38},{"year":2023,"count":33},{"year":2024,"count":29},{"year":2025,"count":15},{"year":2026,"count":15}],"oa_status":"bronze","license":"https://www.springernature.com/gp/researchers/text-and-data-mining","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/emboj.2010.167","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/emboj.2010.167","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Femboj.2010.167","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1038/emboj.2010.167.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1038/emboj.2010.167","host_type":"publisher"},{"url":"https://doi.org/10.1038/emboj.2010.167","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20676056","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2944055","host_type":"repository"},{"url":"https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=6013","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Amyloidosis: Diagnosis, Treatment, Outcomes","S100 Proteins and Annexins","ADAM Proteins","ADAM10 Protein","Amyloid Precursor Protein Secretases","Amyloid beta-Protein Precursor","Animals","Cell Line","Humans","Mass Spectrometry","Membrane Proteins","Mice","Neurons"],"mesh_terms":["ADAM10 Protein","Animals","Cell Line","Humans","Membrane Proteins","Neurons","Mass Spectrometry","Amyloid beta-Protein Precursor","Mice","ADAM Proteins","Amyloid Precursor Protein Secretases"],"keywords":["ADAM10","Proteases","Alpha secretase","Cleavage (geology)","Amyloid precursor protein secretase","Amyloid precursor protein","Biology","Protein precursor","Protease","Cell biology","Biochemistry","Metalloproteinase","Molecular biology","Enzyme","Alzheimer's disease","Disintegrin","Medicine","Internal medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-25T16:58:46.074035Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}