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000271879 1001_ $$0P:(DE-2719)9001406$$aSchröder, Sophie$$b0
000271879 245__ $$aPRDM16-DT is a novel lncRNA that regulates astrocyte function in Alzheimer's disease.
000271879 260__ $$aHeidelberg$$bSpringer$$c2024
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000271879 520__ $$aAstrocytes 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). 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.
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000271879 650_7 $$2Other$$aAlzheimer’s disease
000271879 650_7 $$2Other$$aAstrocyte
000271879 650_7 $$2Other$$aBrain
000271879 650_7 $$2Other$$aLong-non-coding RNA
000271879 650_7 $$2Other$$aPostmortem human brain
000271879 650_7 $$2NLM Chemicals$$aRNA, Long Noncoding
000271879 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000271879 650_7 $$2NLM Chemicals$$aTranscription Factors
000271879 650_7 $$2NLM Chemicals$$aPRDM16 protein, human
000271879 650_7 $$2NLM Chemicals$$aPrdm16 protein, mouse
000271879 650_2 $$2MeSH$$aAstrocytes: metabolism
000271879 650_2 $$2MeSH$$aAstrocytes: pathology
000271879 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000271879 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000271879 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000271879 650_2 $$2MeSH$$aRNA, Long Noncoding: genetics
000271879 650_2 $$2MeSH$$aRNA, Long Noncoding: metabolism
000271879 650_2 $$2MeSH$$aAnimals
000271879 650_2 $$2MeSH$$aHumans
000271879 650_2 $$2MeSH$$aMice
000271879 650_2 $$2MeSH$$aDNA-Binding Proteins: genetics
000271879 650_2 $$2MeSH$$aDNA-Binding Proteins: metabolism
000271879 650_2 $$2MeSH$$aTranscription Factors: genetics
000271879 650_2 $$2MeSH$$aTranscription Factors: metabolism
000271879 650_2 $$2MeSH$$aMale
000271879 650_2 $$2MeSH$$aBrain: metabolism
000271879 650_2 $$2MeSH$$aBrain: pathology
000271879 650_2 $$2MeSH$$aNeurons: metabolism
000271879 650_2 $$2MeSH$$aNeurons: pathology
000271879 650_2 $$2MeSH$$aMice, Inbred C57BL
000271879 7001_ $$0P:(DE-2719)9002371$$aFuchs, Ulrike$$b1
000271879 7001_ $$0P:(DE-2719)9001957$$aGisa, Verena$$b2$$udzne
000271879 7001_ $$0P:(DE-2719)2811063$$aPena, Tonatiuh$$b3
000271879 7001_ $$0P:(DE-2719)2812548$$aKrüger, Dennis M$$b4
000271879 7001_ $$0P:(DE-2719)9003058$$aHempel, Nina$$b5
000271879 7001_ $$0P:(DE-2719)2810773$$aBurkhardt, Susanne$$b6
000271879 7001_ $$aSalinas, Gabriela$$b7
000271879 7001_ $$0P:(DE-2719)2810585$$aSchütz, Anna-Lena$$b8
000271879 7001_ $$aDelalle, Ivana$$b9
000271879 7001_ $$0P:(DE-2719)2811099$$aSananbenesi, Farahnaz$$b10
000271879 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b11$$eLast author
000271879 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-024-02787-x$$gVol. 148, no. 1, p. 32$$n1$$p32$$tActa neuropathologica$$v148$$x0001-6322$$y2024
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