A role for astrocytic miR-129-5p in frontotemporal dementia
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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.
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microRNA‐based predictor for diagnosis of frontotemporal dementia
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- Authors
- Kaurani, L., Pradhan, R., Schröder, S., Burkhardt, S., Schuetz, A.-L., Krüger, D. M., Pena, T., Heutink, P., Sananbenesi, F., & Fischer, A.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Kaurani, Lalit
- Sananbenesi, Farahnaz
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2025-04-11
- Volume
- 15
- Issue
- 1
- Pages
- 142-142
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC11992244
- OpenAlex
- W4409349371
- Semantic Scholar
- 50fc06d0229f425c030c5433e5a3309625501a8f
- Cited by
- 10
- References
- 97
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 1
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (publishedVersion, other-oa)
- DZNE Pub (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (GoBIO miRassay)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- frontotemporal dementia, miR-129-5p, astrocytes, GRN mutations, MAPT mutations, C9orf72 mutation, neuroinflammation, glutamate uptake, neuronal network activity, microRNA dysregulation, therapeutic target
- MeSH terms
- C9orf72 Protein, Progranulins, Aged, Astrocytes, Brain, Female, Humans, Male, Middle Aged, Mutation, tau Proteins, Glutamic Acid, MicroRNAs, Frontotemporal Dementia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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