TY  - JOUR
AU  - Kaurani, Lalit
AU  - Pradhan, Ranjit
AU  - Schröder, Sophie
AU  - Burkhardt, Susanne
AU  - Schuetz, Anna-Lena
AU  - Krüger, Dennis M
AU  - Pena, Tonatiuh
AU  - Heutink, Peter
AU  - Sananbenesi, Farahnaz
AU  - Fischer, Andre
TI  - A role for astrocytic miR-129-5p in frontotemporal dementia.
JO  - Translational Psychiatry
VL  - 15
IS  - 1
SN  - 2158-3188
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2025-00518
SP  - 142
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Frontotemporal Dementia: genetics
KW  - Frontotemporal Dementia: metabolism
KW  - Frontotemporal Dementia: pathology
KW  - Astrocytes: metabolism
KW  - MicroRNAs: genetics
KW  - MicroRNAs: metabolism
KW  - tau Proteins: genetics
KW  - Male
KW  - Female
KW  - C9orf72 Protein: genetics
KW  - Progranulins: genetics
KW  - Middle Aged
KW  - Mutation
KW  - Aged
KW  - Brain: metabolism
KW  - Glutamic Acid: metabolism
KW  - MicroRNAs (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Mirn129 microRNA, human (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
KW  - C9orf72 Protein (NLM Chemicals)
KW  - Progranulins (NLM Chemicals)
KW  - GRN protein, human (NLM Chemicals)
KW  - C9orf72 protein, human (NLM Chemicals)
KW  - Glutamic Acid (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40216778
C2  - pmc:PMC11992244
DO  - DOI:10.1038/s41398-025-03338-y
UR  - https://pub.dzne.de/record/277991
ER  -