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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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lncRNA Glelr modulates microglia inflammatory programs in association with PU.1.
Ranjit Pradhan1, M Sadman Sakib1, Lalit Kaurani1
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Neurobiology of Disease
|March 27, 2026
Summary
Long non-coding RNA (lncRNA) Glelr/GLELR is upregulated in aging brains and linked to Alzheimer's disease. Its depletion in microglia enhances inflammation and phagocytosis, suggesting it as a therapeutic target for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Long non-coding RNAs (lncRNAs) are critical for brain function but their role in microglial aging and neurodegenerative diseases is understudied.
- The non-coding RNAome represents a vast, largely unexplored territory for therapeutic discovery.
Purpose of the Study:
- To investigate the function of the glia-enriched lncRNA Glelr and its human homolog GLELR in microglial aging and neuroinflammation.
- To explore the therapeutic potential of targeting GLELR in neurodegenerative diseases like Alzheimer's disease (AD).
Main Methods:
- Investigated Glelr/GLELR expression in aging astrocytes and microglia.
- Performed knockdown of Glelr in primary microglia and analyzed transcriptional changes via RNA-sequencing.
- Examined conserved functions of human GLELR in induced pluripotent stem cell (iPSC)-derived microglia.
- Analyzed GLELR expression in postmortem Alzheimer's disease brains.
Main Results:
- Glelr/GLELR expression increases with age in microglia and astrocytes.
- Glelr knockdown in microglia enhanced pro-inflammatory cytokine expression (e.g., TNFα) and phagocytic activity.
- RNA-sequencing revealed enrichment of TNF and complement signaling pathways upon Glelr depletion.
- Human GLELR loss in iPSC-derived microglia mirrored these inflammatory and phagocytic changes.
- Glelr interacts with the transcription factor PU.1, influencing its transcriptional programs.
- GLELR expression was significantly reduced in Alzheimer's disease brains.
Conclusions:
- Glelr/GLELR is a conserved, aging-associated lncRNA that regulates microglial inflammatory states via PU.1 interaction.
- Reduced GLELR expression in Alzheimer's disease brains links glial lncRNA dysregulation to neuroinflammation.
- GLELR represents a potential molecular target for modulating microglial activity in neurodegenerative conditions.
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