Year: 2025
Type: article
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.
Source: Translational Psychiatry
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Awards: JPND Verbundprojekt RiMod-FTD: Risikofaktoren und modifizierende Mechanismen bei Fronto-Temporaler Demenz, G2590009325, EPINEURODEVO - Interdisziplinäre Plattform zur Therapieentwicklung bei neurobiologischen Entwicklungsstörungen mit epigenetischem Hintergrund - Teilprojekt: Analyse der Chromatin-Struktur und Genexpression in Modellen für neurobiologische Entwicklungsstörungen, G3445732291, G5131877326, Longitudinale Veränderungen der Gesamtheit kleiner RNAs in der transdiagnostinschen PsyCourse Studie, G584537252, EXC 2067: Multiscale Bioimaging: Von molekularen Maschinen zu Netzwerken erregbarer Zellen, G7987891391
OpenAlex ID: W4409349371