PRDM16-DT: A Brain and Astrocyte-Specific lncRNA Implicated in Alzheimer's Disease.

Autor:	Schröder S; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Fuchs U; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Gisa V; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Pena T; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.; Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Krüger DM; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.; Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Hempel N; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Burkhardt S; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany., Salinas G; NGS- Integrative Genomics Core Unit, Institute of Pathology, University Medical Center Göttingen, Germany., Schütz AL; Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany., Delalle I; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 670 Albany Street, Boston, MA 02118, USA., Sananbenesi F; Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany., Fischer A; Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.; Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 01. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1101/2024.06.27.600964
Abstrakt:	Astrocytes provide crucial support for neurons, contributing to synaptogenesis, synaptic maintenance, and neurotransmitter recycling. Under pathological conditions, deregulation of astrocytes contributes to neurodegenerative diseases such as Alzheimer's disease (AD), highlighting the growing interest in targeting astrocyte function to address early phases of AD pathogenesis. While most research in this field has focused on protein-coding genes, non-coding RNAs, particularly long non-coding RNAs (lncRNAs), have emerged as significant regulatory molecules. In this study, we identified the lncRNA PRDM16-DT as highly enriched in the human brain, where it is almost exclusively expressed in astrocytes. PRDM16-DT and its murine homolog, Prdm16os , are downregulated in the brains of AD patients and in AD models. In line with this, knockdown of PRDM16-DT and Prdm16os revealed its critical role in maintaining astrocyte homeostasis and supporting neuronal function by regulating genes essential for glutamate uptake, lactate release, and neuronal spine density through interactions with the RE1-Silencing Transcription factor (Rest) and Polycomb Repressive Complex 2 (PRC2). Notably, CRISPR-mediated overexpression of Prdm16os mitigated functional deficits in astrocytes induced by stimuli linked to AD pathogenesis. These findings underscore the importance of PRDM16-DT in astrocyte function and its potential as a novel therapeutic target for neurodegenerative disorders characterized by astrocyte dysfunction. Competing Interests: Conflict of interest The authors declare no conflict of interest
Databáze:	MEDLINE
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