{"doi":"10.1016/j.celrep.2025.116561","title":"Control of aging-associated neurodegeneration via hypothalamic extracellular vesicles containing parathymosin","abstract":"Aging-associated neurodegeneration underlies various neurological diseases; however, the neurocrine basis remains poorly understood. Here, we investigate the role of parathymosin (PTMS), a secretory protein with nuclear functions that has recently been identified as a circulating factor in the brain. The results show that loss of PTMS is sufficient to cause severe, age-dependent neurodegeneration and reduced lifespan, whereas hypothalamic PTMS gain of function counteracts aging-associated brain disorders and extends lifespan. PTMS is present in hypothalamic extracellular vesicles (EVs), particularly in subpopulations released by hypothalamic neural stem/progenitor cells (htNSCs). These htNSC-derived EVs carry small nuclear and nucleolar RNAs in a PTMS-associated manner to protect recipient neurons from DNA damage. Therapeutically, these htNSC-derived EVs provide a strong effect against neurodegenerative disorders associated with PTMS deficiency in mouse models, including Alzheimer's disease (AD)-like phenotypes in the 5xFAD model. In conclusion, PTMS possesses anti-neurodegenerative properties, and PTMS-containing hypothalamic EVs are significant in combating aging-associated neurodegenerative diseases.","journal":"Cell Reports","year":2025,"id":548609,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":445769,"name":"Bin Yu","orcid":"0000-0001-7796-7314","position":1,"is_corresponding":false},{"id":1258192,"name":"Yuna Choi","orcid":"0000-0001-5424-2409","position":2,"is_corresponding":false},{"id":1441800,"name":"Gyeongyun Go","orcid":"0000-0002-5813-8745","position":3,"is_corresponding":false},{"id":873682,"name":"Qichao Zhang","orcid":"0000-0003-3492-4482","position":4,"is_corresponding":false},{"id":445770,"name":"Yizhe Tang","orcid":"0000-0001-5354-478X","position":5,"is_corresponding":false},{"id":1168383,"name":"Min Woo Kim","orcid":"0000-0001-9526-8373","position":6,"is_corresponding":false},{"id":407494,"name":"Dongsheng Cai","orcid":"0000-0002-0133-2125","position":7,"is_corresponding":false},{"id":1442314,"name":"Hyun-Gug Jung","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41241944","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":[]}