Journal Article

DZNE-2025-00518

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A role for astrocytic miR-129-5p in frontotemporal dementia.

Kaurani, L. (First author)DZNE* ; Pradhan, R.DZNE* ; Schröder, S.DZNE* ; Burkhardt, S.DZNE* ; Schuetz, A.-L.DZNE* ; Krüger, D. M.DZNE* ; Pena, T.DZNE* ; Heutink, P. ; Sananbenesi, F.DZNE* ; Fischer, A. (Last author)DZNE*

2025
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/s41398-025-03338-y

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.

Keyword(s): Humans (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Frontotemporal Dementia: metabolism (MeSH) ; Frontotemporal Dementia: pathology (MeSH) ; Astrocytes: metabolism (MeSH) ; MicroRNAs: genetics (MeSH) ; MicroRNAs: metabolism (MeSH) ; tau Proteins: genetics (MeSH) ; Male (MeSH) ; Female (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Progranulins: genetics (MeSH) ; Middle Aged (MeSH) ; Mutation (MeSH) ; Aged (MeSH) ; Brain: metabolism (MeSH) ; Glutamic Acid: metabolism (MeSH) ; MicroRNAs ; tau Proteins ; Mirn129 microRNA, human ; MAPT protein, human ; C9orf72 Protein ; Progranulins ; GRN protein, human ; C9orf72 protein, human ; Glutamic Acid

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
2. Clinical Dementia Research (Göttingen) (Clinical Dementia Research (Göttingen))
3. Genome Dynamics in Neurodegenerative Diseases (AG Sananbenesi)
4. Bioinformatics and Genome Dynamics Core (Göttingen) (Bioinformatics Unit (Göttingen))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
3. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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