{"doi":"10.2174/156720508783954695","title":"Assembly, Maturation, and Trafficking of the γ-Secretase Complex in Alzheimers Disease","abstract":null,"journal":"Current Alzheimer Research","year":2008,"id":617721,"datarank":4.376122920257616,"base_score":4.77912349311153,"endowment":4.77912349311153,"self_citation_contribution":0.7168685239667295,"citation_network_contribution":3.6592543962908866,"self_endowment_contribution":0.7168685239667295,"citer_contribution":3.6592543962908866,"corpus_percentile":null,"corpus_rank":null,"citation_count":118,"citer_count":113,"citers_with_citation_signal":99,"citers_with_endowment":99,"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":1198863,"name":"Gang Yu","orcid":"0000-0002-8136-2307","position":1,"is_corresponding":false},{"id":1593153,"name":"Daniel Dries","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Assembly, Maturation, and Trafficking of the γ-Secretase Complex in Alzheimers Disease","abstract":"In this review, we discuss the biology of gamma-secretase, an enigmatic enzyme complex that is responsible for the generation of the amyloid-beta peptide that constitutes the amyloid plaques of Alzheimer's disease. We begin with a brief review on the processing of the amyloid precursor protein and a brief discussion on the family of enzymes involved in regulated intramembrane proteolysis, of which gamma-secretase is a member. We then identify the four major components of the gamma-secretase complex - presenilin, nicastrin, Aph-1, and Pen-2 - with a focus on the identification of each and the role that each plays in the maturation and activity of the complex. We also discuss two new proteins that may play a role in modulating the assembly and activity of the gamma-secretase complex. Next, we summarize the known subcellular locations of each gamma-secretase component and the sites of gamma-secretase activity, as defined by the production of Abeta. Finally, we close by synthesizing all of the included topics into an overarching model for the assembly and trafficking of the gamma-secretase complex, which serves as a launching point for further questions into the biology and function of gamma-secretase in Alzheimer's disease.","is_dataset_classified":null,"base_score":4.77912349311153,"endowment":4.77912349311153,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18393798","pmcid":"PMC2474811","openalex_id":"https://openalex.org/W1973939238","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"R01 AG023104","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG029547","title":null},{"funder_name":"NIA NIH HHS","grant_id":"F32 AG031625","title":null}],"total_grants":3,"fwci":4.5236,"citation_percentile":0.94852166,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":5},{"year":2014,"count":9},{"year":2015,"count":11},{"year":2016,"count":6},{"year":2017,"count":9},{"year":2018,"count":5},{"year":2019,"count":4},{"year":2020,"count":9},{"year":2021,"count":7},{"year":2022,"count":4},{"year":2023,"count":6},{"year":2024,"count":2},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://www.eurekaselect.com/article/27409","host_type":"journal"},{"url":"http://www.eurekaselect.com/article/27409","host_type":"publisher"},{"url":"http://eurekaselect.com/article/download/82433","host_type":"publisher"},{"url":"https://doi.org/10.2174/156720508783954695","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18393798","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2474811","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Prion Diseases and Protein Misfolding","Nuclear Receptors and Signaling","Alzheimer Disease","Amyloid Precursor Protein Secretases","Amyloid beta-Protein Precursor","Animals","Humans","Peptide Hydrolases","Protein Conformation"],"mesh_terms":["Alzheimer Disease","Animals","Humans","Peptide Hydrolases","Protein Conformation","Amyloid beta-Protein Precursor","Amyloid Precursor Protein Secretases"],"keywords":["Alzheimer's disease","Disease","Neuroscience","Psychiatry","Medicine","Chemistry","Psychology","Internal medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T02:28:07.152374Z","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":[]}