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@ARTICLE{Kaurani:277991,
author = {Kaurani, Lalit and Pradhan, Ranjit and Schröder, Sophie
and Burkhardt, Susanne and Schuetz, Anna-Lena and Krüger,
Dennis M and Pena, Tonatiuh and Heutink, Peter and
Sananbenesi, Farahnaz and Fischer, Andre},
title = {{A} role for astrocytic mi{R}-129-5p in frontotemporal
dementia.},
journal = {Translational Psychiatry},
volume = {15},
number = {1},
issn = {2158-3188},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DZNE-2025-00518},
pages = {142},
year = {2025},
abstract = {Frontotemporal dementia is a debilitating neurodegenerative
disorder characterized by frontal and temporal lobe
degeneration, resulting in behavioral changes, language
difficulties, and cognitive decline. In this study, smallRNA
sequencing was conducted on postmortem brain tissues
obtained from the frontal and temporal of FTD patients with
GRN, MAPT, or C9ORF72 mutations. Our analysis identified
miR-129-5p as consistently deregulated across all analyzed
mutation conditions and brain regions. Functional
investigations in in-vitro models revealed a novel role of
miR-129-5p in astrocytes, where its loss led to
neuroinflammation and impaired neuronal support functions,
including reduced glutamate uptake. Depletion of miR-129-5p
in astrocytes also resulted in the loss of neuronal spines
and altered neuronal network activity in a cell culture
system. These findings highlight miR-129-5p as a potential
therapeutic target in neurodegenerative diseases and also
sheds light on the role of astrocytes in Frontotemporal
dementia pathogenesis.},
keywords = {Humans / Frontotemporal Dementia: genetics / Frontotemporal
Dementia: metabolism / Frontotemporal Dementia: pathology /
Astrocytes: metabolism / MicroRNAs: genetics / MicroRNAs:
metabolism / tau Proteins: genetics / Male / Female /
C9orf72 Protein: genetics / Progranulins: genetics / Middle
Aged / Mutation / Aged / Brain: metabolism / Glutamic Acid:
metabolism / MicroRNAs (NLM Chemicals) / tau Proteins (NLM
Chemicals) / Mirn129 microRNA, human (NLM Chemicals) / MAPT
protein, human (NLM Chemicals) / C9orf72 Protein (NLM
Chemicals) / Progranulins (NLM Chemicals) / GRN protein,
human (NLM Chemicals) / C9orf72 protein, human (NLM
Chemicals) / Glutamic Acid (NLM Chemicals)},
cin = {AG Fischer / Clinical Dementia Research (Göttingen) / AG
Sananbenesi / Bioinformatics Unit (Göttingen)},
ddc = {610},
cid = {I:(DE-2719)1410002 / I:(DE-2719)1440015 /
I:(DE-2719)1410004 / I:(DE-2719)1440016},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353) / 899 - ohne Topic
(POF4-899)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353 /
G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40216778},
pmc = {pmc:PMC11992244},
doi = {10.1038/s41398-025-03338-y},
url = {https://pub.dzne.de/record/277991},
}