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ARSACS is caused by mutations in the SACS gene that lead to truncated or defective forms of the 520 kDa multidomain protein, sacsin. Sacsin function is exclusively studied on neuronal cells, where it regulates mitochondrial network organization and facilitates the normal polymerization of neuronal intermediate filaments (i.e., neurofilaments and vimentin). Here, we show that sacsin is also highly expressed in astrocytes, C6 rat glioma cells and N9 mouse microglia. Sacsin knockout in C6 cells (C6Sacs\u2212\/\u2212) induced the accumulation of the glial intermediate filaments glial fibrillary acidic protein (GFAP), nestin and vimentin in the juxtanuclear area, and a concomitant depletion of mitochondria. C6Sacs\u2212\/\u2212 cells showed impaired responses to oxidative challenges (Rotenone) and inflammatory stimuli (Interleukin-6). GFAP aggregation is also associated with other neurodegenerative conditions diagnosed in infants, such as Alexander disease or Giant Axonal Neuropathy. Our results, and the similarities between these disorders, reinforce the possible connection between ARSACS and intermediate filament-associated diseases and point to a potential role of glia in ARSACS pathology.<\/jats:p>","DOI":"10.3390\/cells11020299","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sacsin Deletion Induces Aggregation of Glial Intermediate Filaments"],"prefix":"10.3390","volume":"11","author":[{"given":"Fernanda","family":"Murtinheira","sequence":"first","affiliation":[{"name":"Biosystems & Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1649-004 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Migueis","sequence":"additional","affiliation":[{"name":"Biosystems & Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1649-004 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-7110","authenticated-orcid":false,"given":"Ricardo","family":"Letra-Vilela","sequence":"additional","affiliation":[{"name":"Biosystems & Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1649-004 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, 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Universidad de Oviedo, 33006 Oviedo, Spain"},{"name":"Departamento de Morfolog\u00eda y Biolog\u00eda Celular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-2529","authenticated-orcid":false,"given":"Vanesa","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA), Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain"},{"name":"Departamento de Morfolog\u00eda y Biolog\u00eda Celular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-9353","authenticated-orcid":false,"given":"Federico","family":"Herrera","sequence":"additional","affiliation":[{"name":"Biosystems & Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1649-004 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