000277991 001__ 277991 000277991 005__ 20250504001146.0 000277991 0247_ $$2doi$$a10.1038/s41398-025-03338-y 000277991 0247_ $$2pmid$$apmid:40216778 000277991 0247_ $$2pmc$$apmc:PMC11992244 000277991 0247_ $$2altmetric$$aaltmetric:176247944 000277991 037__ $$aDZNE-2025-00518 000277991 041__ $$aEnglish 000277991 082__ $$a610 000277991 1001_ $$0P:(DE-2719)2812832$$aKaurani, Lalit$$b0$$eFirst author 000277991 245__ $$aA role for astrocytic miR-129-5p in frontotemporal dementia. 000277991 260__ $$aLondon$$bNature Publishing Group$$c2025 000277991 3367_ $$2DRIVER$$aarticle 000277991 3367_ $$2DataCite$$aOutput Types/Journal article 000277991 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1745919408_15704 000277991 3367_ $$2BibTeX$$aARTICLE 000277991 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000277991 3367_ $$00$$2EndNote$$aJournal Article 000277991 520__ $$aFrontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained from the frontal and temporal of FTD patients with GRN, MAPT, or C9ORF72 mutations. Our analysis identified miR-129-5p as consistently deregulated across all analyzed mutation conditions and brain regions. Functional investigations in in-vitro models revealed a novel role of miR-129-5p in astrocytes, where its loss led to neuroinflammation and impaired neuronal support functions, including reduced glutamate uptake. Depletion of miR-129-5p in astrocytes also resulted in the loss of neuronal spines and altered neuronal network activity in a cell culture system. These findings highlight miR-129-5p as a potential therapeutic target in neurodegenerative diseases and also sheds light on the role of astrocytes in Frontotemporal dementia pathogenesis. 000277991 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000277991 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x1 000277991 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x2 000277991 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000277991 650_7 $$2NLM Chemicals$$aMicroRNAs 000277991 650_7 $$2NLM Chemicals$$atau Proteins 000277991 650_7 $$2NLM Chemicals$$aMirn129 microRNA, human 000277991 650_7 $$2NLM Chemicals$$aMAPT protein, human 000277991 650_7 $$2NLM Chemicals$$aC9orf72 Protein 000277991 650_7 $$2NLM Chemicals$$aProgranulins 000277991 650_7 $$2NLM Chemicals$$aGRN protein, human 000277991 650_7 $$2NLM Chemicals$$aC9orf72 protein, human 000277991 650_7 $$03KX376GY7L$$2NLM Chemicals$$aGlutamic Acid 000277991 650_2 $$2MeSH$$aHumans 000277991 650_2 $$2MeSH$$aFrontotemporal Dementia: genetics 000277991 650_2 $$2MeSH$$aFrontotemporal Dementia: metabolism 000277991 650_2 $$2MeSH$$aFrontotemporal Dementia: pathology 000277991 650_2 $$2MeSH$$aAstrocytes: metabolism 000277991 650_2 $$2MeSH$$aMicroRNAs: genetics 000277991 650_2 $$2MeSH$$aMicroRNAs: metabolism 000277991 650_2 $$2MeSH$$atau Proteins: genetics 000277991 650_2 $$2MeSH$$aMale 000277991 650_2 $$2MeSH$$aFemale 000277991 650_2 $$2MeSH$$aC9orf72 Protein: genetics 000277991 650_2 $$2MeSH$$aProgranulins: genetics 000277991 650_2 $$2MeSH$$aMiddle Aged 000277991 650_2 $$2MeSH$$aMutation 000277991 650_2 $$2MeSH$$aAged 000277991 650_2 $$2MeSH$$aBrain: metabolism 000277991 650_2 $$2MeSH$$aGlutamic Acid: metabolism 000277991 7001_ $$0P:(DE-2719)9001438$$aPradhan, Ranjit$$b1$$udzne 000277991 7001_ $$0P:(DE-2719)9001406$$aSchröder, Sophie$$b2 000277991 7001_ 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