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Defects in protein homeostasis frequently lead to neuronal dysfunction and neurological disorders. Given their extreme morphological complexity and high compartmentalization, neurones highly depend on the asymmetrical distribution of their proteome. The common belief is that proteins that sustain axonal, dendritic and synaptic functions are synthesized in the soma and then transported to distal neuronal compartments. However, there is a complementary mechanism by which the mRNAs, and not the proteins, are transported to distal subneuronal domains, and once they reach their destination, they are locally translated. Although once considered heretical, local translation (or local protein synthesis) is now widely accepted by the scientific community. Nonetheless, there is one question that remains largely unexplored in the field, and that is whether local translation in dendrites, axons and synapses is fully regulated by the neurone itself or if non\u2010neuronal cells (e.g., glia) can modulate this mechanism in a non\u2010cell\u2010autonomous manner. Here, we combined primary neuronal cultures, astrocyte\u2010derived extracellular vesicle (EVs) isolation, and proteomics to investigate whether astroglial EVs modulate local translation in axons. We show that EVs released by astrocytes exposed to amyloid\u2010\u03b2 peptide (A\u03b2) enhance protein synthesis specifically in distal axons and increase synaptic integrity. Proteomics analysis and western blotting identified the ribosomal protein Rps6 as an astroglial A\u03b2\u2010EV cargo delivered to axons. Interestingly, genetic downregulation revealed the contribution of vesicular Rps6 to translation regulation in axons and synaptic integrity. To our knowledge, this is the first report that directly demonstrates glial control of local translation in neurones through EVs, revealing a novel glia\u2010to\u2010neurone communication mechanism in an experimental model of Alzheimer's disease (AD).<\/jats:p>","DOI":"10.1002\/jev2.70216","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:10:58Z","timestamp":1766157058000},"source":"Crossref","is-referenced-by-count":3,"title":["Vesicular Rps6 Released by Astrocytes in an Experimental Model of AD Regulates Local Translation and Enhances Synaptic Integrity in Neurones"],"prefix":"10.1002","volume":"14","author":[{"given":"Mar\u00eda","family":"Gamarra","sequence":"first","affiliation":[{"name":"Achucarro Basque Center for Neuroscience  Leioa Spain"},{"name":"Departamento de Neurociencias Universidad del Pa\u00eds Vasco (UPV\/EHU)  Leioa Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa  Madrid 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Technology Alliance (BRTA)  Derio, Bizkaia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"},{"name":"IKERBASQUE Basque Foundation for Science  Bilbao Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9628-4631","authenticated-orcid":false,"given":"Jimena","family":"Baleriola","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience  Leioa Spain"},{"name":"Departamento de Neurociencias Universidad del Pa\u00eds Vasco (UPV\/EHU)  Leioa Spain"},{"name":"IKERBASQUE Basque Foundation for Science  Bilbao Spain"},{"name":"Cajal Neuroscience Center\u2010CSIC  Madrid 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