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@ARTICLE{Pradhan:286089,
      author       = {Pradhan, Ranjit and Sakib, M Sadman and Kaurani, Lalit and
                      Krüger, Dennis M and Pena, Tonatiuh and Burkhardt, Susanne
                      and Schütz, Anna-Lena and Kronenberg-Versteeg, Deborah and
                      Delalle, Ivana and Sananbenesi, Farahnaz and Fischer, Andre},
      title        = {lnc{RNA} {G}lelr modulates microglia inflammatory programs
                      in association with {PU}.1.},
      journal      = {Neurobiology of disease},
      volume       = {222},
      issn         = {0969-9961},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2026-00385},
      pages        = {107366},
      year         = {2026},
      abstract     = {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.},
      keywords     = {RNA, Long Noncoding: metabolism / RNA, Long Noncoding:
                      genetics / Microglia: metabolism / Animals / Humans / Mice /
                      Trans-Activators: metabolism / Trans-Activators: genetics /
                      Proto-Oncogene Proteins: metabolism / Proto-Oncogene
                      Proteins: genetics / Inflammation: metabolism /
                      Inflammation: genetics / Mice, Inbred C57BL / Cells,
                      Cultured / Aging: metabolism / Astrocytes: metabolism /
                      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)},
      cin          = {AG Fischer / Bioinformatics Unit (Göttingen) / AG
                      Sananbenesi / AG Kronenberg-Versteeg},
      ddc          = {570},
      cid          = {I:(DE-2719)1410002 / I:(DE-2719)1440016 /
                      I:(DE-2719)1410004 / I:(DE-2719)1210015},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
                      (POF4-351) / 899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351 /
                      G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41895620},
      doi          = {10.1016/j.nbd.2026.107366},
      url          = {https://pub.dzne.de/record/286089},
}