{"doi":"10.2174/156802608783334060","title":"Activity of γ -Secretase on Substrates Other than APP","abstract":null,"journal":"Current Topics in Medicinal Chemistry","year":2008,"id":635243,"datarank":0.6329261557764161,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":0.0,"self_endowment_contribution":0.6329261557764161,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1648012,"name":"Alberto D.","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Activity of γ -Secretase on Substrates Other than APP","abstract":"Gamma-secretase is an intramembranous protein complex that cleaves many type-I membrane proteins, including the Notch receptor and the beta-amyloid precursor protein (APP). Interest in gamma-secretase comes, in part, from the fact that this multiprotein complex is responsible for the cleavage of APP that generates the amyloid-beta peptide (Abeta), one of the primary components of amyloid plaques in Alzheimer's disease (AD). Over the last years, molecular identification of the complex has shown that gamma-secretase is an aspartyl protease composed of four different members that are essential for the enzymatic activity: presenilin 1, aph1, pen-2 and nicastrin. In recent years, an increasing number of type-I membrane proteins have been shown to be cleaved by gamma-secretase. How the enzyme cleaves such a set of substrates with diverse functions and subcellular localizations is not well understood. In overexpression assays, the gamma-secretase cleavage of some substrates releases intracellular domains with signaling properties. On the other hand, the loose specificity required for intramembrane cleavage has raised the possibility of gamma-secretase as the membrane proteasome. The impact of gamma-secretase on other substrates has clear implications for the development of new therapies for AD, and in particular for the search of gamma-secretase inhibitors or modulators. Interference with the cleavage of some of the gamma-secretase substrates has been shown to be associated with serious adverse effects in animal models. The understanding of the mechanism by which gamma-secretase recognizes and cleaves all these proteins is of great importance to clarify the function of gamma-secretase and its role as a therapeutic target in AD, and possibly in other diseases in which gamma-secretase is involved.","is_dataset_classified":null,"base_score":4.219507705176107,"endowment":4.219507705176107,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18220928","pmcid":null,"openalex_id":"https://openalex.org/W22223414","authors":[],"funders":[],"total_grants":0,"fwci":6.0315,"citation_percentile":0.96840018,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":2},{"year":2014,"count":4},{"year":2015,"count":2},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":2},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://eurekaselect.com/article/download/82095","host_type":"publisher"},{"url":"https://doi.org/10.2174/156802608783334060","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18220928","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Cholinesterase and Neurodegenerative Diseases","Enzyme Production and Characterization","Amyloid Precursor Protein Secretases","Amyloid beta-Protein Precursor","Animals","Cell Adhesion","Humans","Protein Binding","Receptors, Notch","Substrate Specificity"],"mesh_terms":["Animals","Cell Adhesion","Humans","Protein Binding","Substrate Specificity","Amyloid beta-Protein Precursor","Receptors, Notch","Amyloid Precursor Protein Secretases"],"keywords":["Nicastrin","Presenilin","Gamma secretase","Alpha secretase","Amyloid precursor protein","Amyloid precursor protein secretase","Chemistry","Cell biology","P3 peptide","Cleavage (geology)","Biochemistry","Membrane protein","Alzheimer's disease","Biology","Membrane"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:50:27.571219Z","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":[]}