{"doi":"10.1101/2021.04.16.440151","title":"Extracellular Hsp90α Detoxifies β-Amyloid Fibrils Through an NRF2 and Autophagy Dependent Pathway","abstract":"Abstract We have investigated the role of e xtracellular H eat s hock p rotein 90 alpha (eHsp90α) in conferring protection of neuronal cells against fibrillary amyloid beta (f-Aβ 1-42 ) toxicity mediated by microglial cells. Formation of f-Aβ 1-42 plaques leads to neurotoxic inflammation, a critical pathological feature of Alzheimer’s Disease. We observed increased uptake and clearance of internalized f-Aβ 1-42 by microglial cells treated with eHsp90α, an effect associated with activation of NRF2 (NF-E2-related factor 2) - mediated autophagy. eHsp90α thus mitigated the neuronal toxicity of f-Aβ 1-42 -activated microglia. In addition, eHsp90α facilitated f-Aβ 1-42 engulfment by microglial cells in vitro . In summary, eHsp90α triggers NRF2-mediated autophagy in microglia and thus protects against the neurotoxic effects of f-Aβ 1-42 .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218601,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":393573,"name":"Benjamin Lang","orcid":"0000-0002-2205-8591","position":1,"is_corresponding":false},{"id":282633,"name":"Thiago J. Borges","orcid":"0000-0002-6554-0169","position":2,"is_corresponding":false},{"id":566325,"name":"Yuka Okusha","orcid":"0000-0002-1399-2294","position":3,"is_corresponding":false},{"id":816732,"name":"Sachin Doshi","orcid":null,"position":4,"is_corresponding":false},{"id":816733,"name":"Suraya Yasmine","orcid":null,"position":5,"is_corresponding":false},{"id":816383,"name":"Joanne Clark","orcid":"0000-0002-9335-0282","position":6,"is_corresponding":false},{"id":316339,"name":"Reeham Choudhury","orcid":null,"position":7,"is_corresponding":false},{"id":427992,"name":"Lay‐Hong Ang","orcid":"0000-0002-2425-7746","position":8,"is_corresponding":false},{"id":288924,"name":"Maya E. Woodbury","orcid":"0000-0003-0613-0220","position":9,"is_corresponding":false},{"id":236493,"name":"Tsuneya Ikezu","orcid":"0000-0002-3979-8596","position":10,"is_corresponding":false},{"id":393574,"name":"Stuart K. Calderwood","orcid":"0000-0001-9966-3354","position":11,"is_corresponding":false},{"id":393571,"name":"Ayesha Murshid","orcid":"0000-0002-3331-5960","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:53:29.626149Z","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":[]}