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@ARTICLE{Schrder:271879,
author = {Schröder, Sophie and Fuchs, Ulrike and Gisa, Verena and
Pena, Tonatiuh and Krüger, Dennis M and Hempel, Nina and
Burkhardt, Susanne and Salinas, Gabriela and Schütz,
Anna-Lena and Delalle, Ivana and Sananbenesi, Farahnaz and
Fischer, Andre},
title = {{PRDM}16-{DT} is a novel lnc{RNA} that regulates astrocyte
function in {A}lzheimer's disease.},
journal = {Acta neuropathologica},
volume = {148},
number = {1},
issn = {0001-6322},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2024-01091},
pages = {32},
year = {2024},
abstract = {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). 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.},
keywords = {Astrocytes: metabolism / Astrocytes: pathology / Alzheimer
Disease: genetics / Alzheimer Disease: metabolism /
Alzheimer Disease: pathology / RNA, Long Noncoding: genetics
/ RNA, Long Noncoding: metabolism / Animals / Humans / Mice
/ DNA-Binding Proteins: genetics / DNA-Binding Proteins:
metabolism / Transcription Factors: genetics / Transcription
Factors: metabolism / Male / Brain: metabolism / Brain:
pathology / Neurons: metabolism / Neurons: pathology / Mice,
Inbred C57BL / Alzheimer’s disease (Other) / Astrocyte
(Other) / Brain (Other) / Long-non-coding RNA (Other) /
Postmortem human brain (Other) / RNA, Long Noncoding (NLM
Chemicals) / DNA-Binding Proteins (NLM Chemicals) /
Transcription Factors (NLM Chemicals) / PRDM16 protein,
human (NLM Chemicals) / Prdm16 protein, mouse (NLM
Chemicals)},
cin = {AG Fischer / AG Sananbenesi / Bioinformatics Unit
(Göttingen)},
ddc = {610},
cid = {I:(DE-2719)1410002 / I:(DE-2719)1410004 /
I:(DE-2719)1440016},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11362476},
pubmed = {pmid:39207536},
doi = {10.1007/s00401-024-02787-x},
url = {https://pub.dzne.de/record/271879},
}