{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:05:56Z","timestamp":1791918356480,"version":"4.3.4"},"reference-count":56,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011513","name":"Ataxia Canada","doi-asserted-by":"crossref","award":["56220"],"award-info":[{"award-number":["56220"]}],"id":[{"id":"10.13039\/100011513","id-type":"DOI","asserted-by":"crossref"}]},{"name":"IRCCS Ospedale San Raffaele"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. Although several studies have highlighted cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary cerebellar astrocytes with an RNA interference-based approach, to achieve a reduction of FXN comparable to that observed in individuals with FRDA. These FRDA-like astrocytes display some typical features of the disease, such as an increase of oxidative stress and a depletion of glutathione content. Moreover, FRDA-like astrocytes exhibit decreased Ca2+ responses to purinergic stimuli. Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, likely impairing their complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators in a Ca2+-dependent manner could affect neuronal function, contributing to neurodegeneration.<\/jats:p>","DOI":"10.1242\/jcs.263446","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T09:21:33Z","timestamp":1733736093000},"source":"Crossref","is-referenced-by-count":6,"title":["Altered Ca2+ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes"],"prefix":"10.1242","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7144-582X","authenticated-orcid":false,"given":"Chiara","family":"Marullo","sequence":"first","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute 1 Division of Neuroscience , , 20132 Milan 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Division of Neuroscience , , 20132 Milan ,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 Faculty of Medicine and Surgery , , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4594-6273","authenticated-orcid":false,"given":"Gian Giacomo","family":"Consalez","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute 1 Division of Neuroscience , , 20132 Milan ,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 Faculty of Medicine and Surgery , , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-8612","authenticated-orcid":false,"given":"Franca","family":"Codazzi","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute 1 Division of Neuroscience , , 20132 Milan ,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 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