286089 20260413125613.0 10.1016/j.nbd.2026.107366 doi pmid:41895620 pmid 0969-9961 ISSN 1095-953X ISSN DZNE-2026-00385 English 570 Pradhan, Ranjit P:(DE-2719)9001438 0 First author dzne lncRNA Glelr modulates microglia inflammatory programs in association with PU.1. [Amsterdam] 2026 Elsevier article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1776077607_32197 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Long non-coding RNAs (lncRNAs) are emerging as key regulators of brain function, but their contribution to microglial aging and neurodegenerative disease remains largely unknown. Because only 1.5% of the human genome encodes proteins, whereas the vast majority of transcripts belong to the largely unexplored non-coding RNAome, elucidating the functions of non-coding RNAs provides an unprecedented opportunity to expand the space for therapeutic discovery. We recently identified the glia-enriched lncRNA Glelr as upregulated in the aging mouse hippocampus. Here, we investigated its function in microglia and its human homolog GLELR. We found that Glelr/GLELR is expressed in both astrocytes and microglia and increases with age. Knockdown of Glelr in primary microglia led to enhanced expression of pro-inflammatory cytokines, including TNFα, and increased phagocytic activity. RNA-sequencing revealed widespread transcriptional changes enriched for TNF and complement signaling pathways. The human homolog GLELR showed conserved functions in iPSC-derived microglia, where its loss similarly promoted inflammatory gene expression and phagocytosis. Mechanistically, Glelr interacts with the microglial transcription factor PU.1, and its depletion overlapped with PU.1-driven transcriptional programs. Consistent with these findings, GLELR expression was significantly reduced in postmortem Alzheimer's disease (AD) brains, and AD-associated genes were enriched among Glelr-regulated targets. Together, our results identify Glelr/GLELR as a conserved, aging-associated lncRNA that modulates microglial inflammatory states through interaction with PU.1. This work links glial lncRNA regulation to AD-related neuroinflammation and suggests GLELR as a potential molecular target to fine-tune microglial activity in neurodegenerative diseases. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 1 899 - ohne Topic (POF4-899) G:(DE-HGF)POF4-899 POF4-899 POF IV 2 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 3222401L13Rik/ENSG00000272070 Other Alzheimer's disease Other Long non-coding RNA (lncRNA) Other Microglia Other Neuroinflammation Other Non-coding RNAome Other PU.1 (SPI1) Other RNA, Long Noncoding NLM Chemicals Trans-Activators NLM Chemicals Proto-Oncogene Proteins NLM Chemicals RNA, Long Noncoding: metabolism MeSH RNA, Long Noncoding: genetics MeSH Microglia: metabolism MeSH Animals MeSH Humans MeSH Mice MeSH Trans-Activators: metabolism MeSH Trans-Activators: genetics MeSH Proto-Oncogene Proteins: metabolism MeSH Proto-Oncogene Proteins: genetics MeSH Inflammation: metabolism MeSH Inflammation: genetics MeSH Mice, Inbred C57BL MeSH Cells, Cultured MeSH Aging: metabolism MeSH Astrocytes: metabolism MeSH Sakib, M Sadman P:(DE-2719)2812054 1 dzne Kaurani, Lalit P:(DE-2719)2812832 2 dzne Krüger, Dennis M P:(DE-2719)2812548 3 dzne Pena, Tonatiuh P:(DE-2719)2811063 4 dzne Burkhardt, Susanne P:(DE-2719)2810773 5 dzne Schütz, Anna-Lena P:(DE-2719)2810585 6 dzne Kronenberg-Versteeg, Deborah P:(DE-2719)9001451 7 dzne Delalle, Ivana P:(DE-HGF)0 8 Sananbenesi, Farahnaz P:(DE-2719)2811099 9 dzne Fischer, Andre P:(DE-2719)2000047 10 Last author dzne 10.1016/j.nbd.2026.107366 Vol. 222, p. 107366 - PERI:(DE-600)1471408-5 107366 Neurobiology of disease 222 2026 0969-9961 http://pub.dzne.de/record/286089/files/DZNE-2026-00385.pdf Restricted http://pub.dzne.de/record/286089/files/DZNE-2026-00385.pdf?subformat=pdfa pdfa Restricted Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)9001438 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2812054 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2812832 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2812548 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2811063 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2810773 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810585 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)9001451 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)2811099 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2000047 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 1 DE-HGF Programmungebundene Forschung ohne Programm G:(DE-HGF)POF4-890 G:(DE-HGF)POF4-899 G:(DE-HGF)POF4 G:(DE-HGF)POF4-800 G:(DE-HGF)POF ohne Topic 2 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2025-11-11 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2025-11-11 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2025-08-21T14:53:16Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2025-08-21T14:53:16Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2025-08-21T14:53:16Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2025-11-11 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2025-11-11 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2025-11-11 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2025-11-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2025-11-11 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2025-11-11 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2025-11-11 JCR StatID:(DE-HGF)0100 StatID NEUROBIOL DIS : 2022 2025-11-11 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2025-11-11 Peer Review StatID:(DE-HGF)0030 StatID ASC 2025-11-11 IF >= 5 StatID:(DE-HGF)9905 StatID NEUROBIOL DIS : 2022 2025-11-11 Article Processing Charges StatID:(DE-HGF)0561 StatID 2025-11-11 Fees StatID:(DE-HGF)0700 StatID 2025-11-11 I:(DE-2719)1410002 AG Fischer Epigenetics and Systems Medicine in Neurodegenerative Diseases 0 I:(DE-2719)1440016 Bioinformatics Unit (Göttingen) Bioinformatics and Genome Dynamics Core (Göttingen) 1 I:(DE-2719)1410004 AG Sananbenesi Genome Dynamics in Neurodegenerative Diseases 2 I:(DE-2719)1210015 AG Kronenberg-Versteeg Glial Cell Biology 3 journal EDITORS VDBINPRINT I:(DE-2719)1410002 I:(DE-2719)1440016 I:(DE-2719)1410004 I:(DE-2719)1210015 UNRESTRICTED