{"doi":"10.3390/s25113298","title":"Endogenous γ-Secretase Is Linked to Phagocytic Activity in Microglial Cells","abstract":"γ-Secretase has primarily been studied in neurons, whereas increasing evidence highlights its importance in microglia. Previous research has shown that the pharmacological inhibition of γ-secretase impairs microglial phagocytic activity. In this study, we used a genetically encoded Förster resonance energy transfer (FRET)-based biosensor to record γ-secretase activity, aiming to determine if naturally occurring cell-by-cell variations in endogenous γ-secretase activity are associated with phagocytic activity. Using the Notch1 N100 Y-T biosensor, we found that the regulation of endogenous γ-secretase activity varies among individual BV-2 microglial cells. Our multiplexed time-lapse imaging revealed that the phagocytosis of E. coli bioparticles was impaired in cells with lower γ-secretase activity compared to those with higher activity. Complementary biochemical analysis, utilizing Zymosan bioparticles and fluorescence-activated cell sorting (FACS), further demonstrated that cells with reduced phagocytic activity exhibited decreased endogenous γ-secretase activity. Collectively, our confirmatory study supports previous findings that microglial phagocytic activity is closely linked to γ-secretase and emphasizes the essential role of γ-secretase in microglia.","journal":"Sensors","year":2025,"id":566717,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367418,"name":"Mei CQ Houser","orcid":"0009-0003-7590-4290","position":1,"is_corresponding":false},{"id":858630,"name":"Sebastián Torres","orcid":"0000-0002-4900-7161","position":2,"is_corresponding":false},{"id":1471018,"name":"Natalia Wieckiewicz","orcid":null,"position":3,"is_corresponding":false},{"id":1300232,"name":"Michael Sadek","orcid":"0000-0003-0110-2239","position":4,"is_corresponding":false},{"id":1471019,"name":"Midori Yokomizo","orcid":null,"position":5,"is_corresponding":false},{"id":367420,"name":"Masato Maesako","orcid":"0000-0002-1970-2462","position":6,"is_corresponding":false},{"id":1104035,"name":"Emily L. Williams","orcid":"0000-0003-3506-9668","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:56:40.491968Z","pmid":"40968865","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":[]}