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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/225879
Increased translation in adult mouse striatum is sufficient to induce motor dysfunction
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Protein synthesis is a process finely regulated in all cell types but specially in neurons as they need rapid changes in protein concentration for synaptic plasticity. Alterations in translation rates have been shown in diseases affecting the brain. In Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by the presence of motor, cognitive and psychiatric symptoms, we have shown that translation is increased in the striatum contributing to motor symptoms. However, very little is known about how translation modulates motor function in physiological conditions. To study this, we overexpressed a constitutively active mutant form of 4E-BP1 (4E-BP1F113A), a translation repressor, in the striatum of wild-type mice and performed motor tests. One month after striatal injection of adeno-associated viral vectors expressing 4E-BP1F113A, mice exhibited motor symptoms similar to those observed in the R6/1 HD mouse model. Unexpectedly, de novo protein synthesis and 4E-BP1 phosphorylation were enhanced in the striatum of wild-type mice overexpressing 4E-BP1F113A. Moreover, the striatum of these animals showed alterations in protein levels of neuronal markers similar to that observed in HD striatum. Altogether, our results indicate that enhanced protein synthesis in the striatum induces neuronal dysfunction and motor symptoms, and reinforce the idea that increased translation is involved in HD pathogenesis.
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CASTANY PLADEVALL, Carla, CREUS MUNCUNILL, Jordi, BERGÉ-GARDEÑES, Maria, GOLBANO, Arantxa, BRITO, Verónica, PÉREZ NAVARRO, Ester. Increased translation in adult mouse striatum is sufficient to induce motor dysfunction. _Brain Communications_. 2025. Vol. 7, núm. 4, pàgs. fcaf250. [consulta: 29 de gener de 2026]. ISSN: 2632-1297. [Disponible a: https://hdl.handle.net/2445/225879]