{"doi":"10.1126/science.286.5441.916","title":"The Presenilins in Alzheimer's Disease--Proteolysis Holds the Key","abstract":"<jats:p>Alzheimer's disease (AD) research has shown that patients with an inherited form of the disease carry mutations in the presenilin proteins or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-β (the primary component of the amyloid deposits found in AD brains). However, it is not clear how the presenilins contribute to this increase. New findings now show that the presenilins affect APP processing through their effects on γ-secretase, an enzyme that cleaves APP. Also, it is known that the presenilins are involved in the cleavage of the Notch receptor, hinting that they either directly regulate γ-secretase activity or themselves are protease enzymes. These findings suggest that the presenilins may prove to be valuable molecular targets for the development of drugs to combat AD.</jats:p>","journal":"Science","year":1999,"id":27619,"datarank":14.633260600446668,"base_score":5.971261839790462,"endowment":5.971261839790462,"self_citation_contribution":0.8956892759685695,"citation_network_contribution":13.737571324478099,"self_endowment_contribution":0.8956892759685695,"citer_contribution":13.737571324478099,"corpus_percentile":null,"corpus_rank":null,"citation_count":391,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":156875,"name":"Bart De Strooper","orcid":null,"position":1,"is_corresponding":false},{"id":84331,"name":"Christian Haass","orcid":"0000-0002-4869-1627","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.971261839790462,"endowment":5.971261839790462,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10542139","pmcid":null,"openalex_id":"https://openalex.org/W1973130935","authors":[],"funders":[],"total_grants":0,"fwci":19.7688,"citation_percentile":0.99738035,"influential_citations":4,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":14},{"year":2014,"count":18},{"year":2015,"count":10},{"year":2016,"count":6},{"year":2017,"count":7},{"year":2018,"count":9},{"year":2019,"count":5},{"year":2020,"count":5},{"year":2021,"count":11},{"year":2022,"count":5},{"year":2023,"count":7},{"year":2024,"count":7},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.286.5441.916","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.286.5441.916","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10542139","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Prion Diseases and Protein Misfolding","Cellular transport and secretion","Biology","Medicine","Alzheimer Disease","Amyloid Precursor Protein Secretases","Amyloid beta-Protein Precursor","Animals","Aspartic Acid Endopeptidases","Endopeptidases","Humans","Membrane Proteins","Protease Inhibitors","Protein Processing, Post-Translational","Receptors, Notch","Signal Transduction"],"mesh_terms":["Alzheimer Disease","Animals","Humans","Membrane Proteins","Endopeptidases","Protease Inhibitors","Protein Processing, Post-Translational","Signal Transduction","Aspartic Acid Endopeptidases","Amyloid beta-Protein Precursor","Receptors, Notch","Amyloid Precursor Protein Secretases"],"keywords":["Presenilin","Amyloid precursor protein","Proteolysis","Amyloid precursor protein secretase","Alzheimer's disease","Alpha secretase","Disease","Protease","Nicastrin","Enzyme","Neuroscience","Biology","Cell biology","Biochemistry","Medicine","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26743661.v1","title":"Additional file 1 of A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26743661","title":"Additional file 1 of A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T18:44:17.262528Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}