{"doi":"10.1126/sciadv.abb8680","title":"Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer’s disease","abstract":"Myelin degeneration and white matter loss resulting from oligodendrocyte (OL) death are early events in Alzheimer's disease (AD) that lead to cognitive deficits; however, the underlying mechanism remains unknown. Here, we find that mature OLs in both AD patients and an AD mouse model undergo NLR family pyrin domain containing 3 (NLRP3)-dependent Gasdermin D-associated inflammatory injury, concomitant with demyelination and axonal degeneration. The mature OL-specific knockdown of dynamin-related protein 1 (Drp1; a mitochondrial fission guanosine triphosphatase) abolishes NLRP3 inflammasome activation, corrects myelin loss, and improves cognitive ability in AD mice. Drp1 hyperactivation in mature OLs induces a glycolytic defect in AD models by inhibiting hexokinase 1 (HK1; a mitochondrial enzyme that initiates glycolysis), which triggers NLRP3-associated inflammation. These findings suggest that OL glycolytic deficiency plays a causal role in AD development. The Drp1-HK1-NLRP3 signaling axis may be a key mechanism and therapeutic target for white matter degeneration in AD.","journal":"Science Advances","year":2020,"id":50458,"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":193,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":248927,"name":"Rihua Wang","orcid":null,"position":1,"is_corresponding":false},{"id":247911,"name":"Di Hu","orcid":"0000-0003-4047-7340","position":2,"is_corresponding":false},{"id":247912,"name":"Xiaoyan Sun","orcid":"0000-0003-0442-6263","position":3,"is_corresponding":false},{"id":247913,"name":"Hisashi Fujioka","orcid":"0000-0001-8511-7141","position":4,"is_corresponding":false},{"id":247914,"name":"Kathleen C. Lundberg","orcid":"0000-0002-5703-2543","position":5,"is_corresponding":false},{"id":247915,"name":"E. Ricky Chan","orcid":"0000-0001-9277-5329","position":6,"is_corresponding":false},{"id":109757,"name":"QuanQiu Wang","orcid":null,"position":7,"is_corresponding":false},{"id":109147,"name":"Rong Xu","orcid":"0000-0003-3127-4795","position":8,"is_corresponding":false},{"id":93,"name":"Margaret E. Flanagan","orcid":"0009-0008-7078-3545","position":9,"is_corresponding":false},{"id":247916,"name":"Andrew A. Pieper","orcid":"0000-0001-6299-6577","position":10,"is_corresponding":false},{"id":247917,"name":"Xin Qi","orcid":"0000-0002-9578-3890","position":11,"is_corresponding":false},{"id":247910,"name":"Xinwen Zhang","orcid":"0000-0001-7070-8459","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T20:38:25.860949Z","pmid":"33277246","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":[]}