{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:47:33Z","timestamp":1792122453212,"version":"4.4.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation","doi-asserted-by":"publisher","award":["ALG-01- 0145-FEDER-29480"],"award-info":[{"award-number":["ALG-01- 0145-FEDER-29480"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Polyglutamine diseases are a group of neurodegenerative disorders caused by an abnormal expansion of CAG repeat tracts in the codifying regions of nine, otherwise unrelated, genes. While the protein products of these genes are suggested to play diverse cellular roles, the pathogenic mutant proteins bearing an expanded polyglutamine sequence share a tendency to self-assemble, aggregate and engage in abnormal molecular interactions. Understanding the shared paths that link polyglutamine protein expansion to the nervous system dysfunction and the degeneration that takes place in these disorders is instrumental to the identification of targets for therapeutic intervention. Among polyglutamine diseases, spinocerebellar ataxias (SCAs) share many common aspects, including the fact that they involve dysfunction of the cerebellum, resulting in ataxia. Our work aimed at exploring a putative new therapeutic target for the two forms of SCA with higher worldwide prevalence, SCA type 2 (SCA2) and type 3 (SCA3), which are caused by expanded forms of ataxin-2 (ATXN2) and ataxin-3 (ATXN3), respectively. The pathophysiology of polyglutamine diseases has been described to involve an inability to properly respond to cell stress. We evaluated the ability of GTPase-activating protein-binding protein 1 (G3BP1), an RNA-binding protein involved in RNA metabolism regulation and stress responses, to counteract SCA2 and SCA3 pathology, using both in vitro and in vivo disease models. Our results indicate that G3BP1 overexpression in cell models leads to a reduction of ATXN2 and ATXN3 aggregation, associated with a decrease in protein expression. This protective effect of G3BP1 against polyglutamine protein aggregation was reinforced by the fact that silencing G3bp1 in the mouse brain increases human expanded ATXN2 and ATXN3 aggregation. Moreover, a decrease of G3BP1 levels was detected in cells derived from patients with SCA2 and SCA3, suggesting that G3BP1 function is compromised in the context of these diseases. In lentiviral mouse models of SCA2 and SCA3, G3BP1 overexpression not only decreased protein aggregation but also contributed to the preservation of neuronal cells. Finally, in an SCA3 transgenic mouse model with a severe ataxic phenotype, G3BP1 lentiviral delivery to the cerebellum led to amelioration of several motor behavioural deficits. Overall, our results indicate that a decrease in G3BP1 levels may be a contributing factor to SCA2 and SCA3 pathophysiology, and that administration of this protein through viral vector-mediated delivery may constitute a putative approach to therapy for these diseases, and possibly other polyglutamine disorders.<\/jats:p>","DOI":"10.1093\/brain\/awac473","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T17:35:28Z","timestamp":1670952928000},"page":"2346-2363","source":"Crossref","is-referenced-by-count":32,"title":["The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated deficits"],"prefix":"10.1093","volume":"146","author":[{"given":"Rebekah","family":"Koppenol","sequence":"first","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"PhD Program in Biomedial Sciences, Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"PhD Program in Biomedial Sciences, Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas T","family":"Afonso","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Afonso-Reis","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael G","family":"Costa","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Tom\u00e9","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"Teixeira","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana Pinto","family":"da Silva","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"C\u00f4desso","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"PhD Program in Biomedial Sciences, Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David V C","family":"Brito","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-9690","authenticated-orcid":false,"given":"Liliana","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Marcelo","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-3307","authenticated-orcid":false,"given":"Lu\u00eds","family":"Pereira de Almeida","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra , 3004-504 Coimbra , Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra , 3000-548 Coimbra , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A","family":"Matos","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9019-7569","authenticated-orcid":false,"given":"Cl\u00e9vio","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute , 8005-139 Faro , Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve , 8005-139 Faro , Portugal"},{"name":"Champalimaud Research Program, Champalimaud Center for the Unknown , 1400-038 Lisbon , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"2023060100310404900_awac473-B1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/jnc.14541","article-title":"Machado\u2013Joseph disease\/spinocerebellar ataxia type 3: Lessons from disease pathogenesis and clues into therapy","volume":"148","author":"Matos","year":"2019","journal-title":"J Neurochem"},{"key":"2023060100310404900_awac473-B2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng1196-269","article-title":"Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2","volume":"14","author":"Pulst","year":"1996","journal-title":"Nat Genet"},{"key":"2023060100310404900_awac473-B3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng1194-221","article-title":"CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1","volume":"8","author":"Kawaguchi","year":"1994","journal-title":"Nat Genet"},{"key":"2023060100310404900_awac473-B4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pneurobio.2011.06.007","article-title":"Polyglutamine diseases: The special case of ataxin-3 and Machado\u2013Joseph disease","volume":"95","author":"Matos","year":"2011","journal-title":"Prog Neurobiol"},{"key":"2023060100310404900_awac473-B5","doi-asserted-by":"crossref","first-page":"753","DOI":"10.2174\/1381612822666161227121912","article-title":"Proteolytic cleavage of polyglutamine disease-causing proteins: Revisiting the toxic fragment hypothesis","volume":"23","author":"Matos","year":"2017","journal-title":"Curr Pharm Des"},{"key":"2023060100310404900_awac473-B6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/79162","article-title":"Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human","volume":"26","author":"Huynh","year":"2000","journal-title":"Nat Genet"},{"key":"2023060100310404900_awac473-B7","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ana.410430305","article-title":"Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado-Joseph disease","volume":"43","author":"Onodera","year":"1998","journal-title":"Ann Neurol"},{"key":"2023060100310404900_awac473-B8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10059-013-0167-x","article-title":"Aggregation formation in the polyglutamine diseases: Protection at a cost?","volume":"36","author":"Todd","year":"2013","journal-title":"Mol Cells"},{"key":"2023060100310404900_awac473-B9","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1093\/hmg\/ddg151","article-title":"Polyglutamine protein aggregation and toxicity are linked to the cellular stress response","volume":"12","author":"Cowan","year":"2003","journal-title":"Hum Mol Genet"},{"key":"2023060100310404900_awac473-B10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1269\/jrr.09048S","article-title":"Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat","volume":"50","author":"Takahashi","year":"2009","journal-title":"J Radiat Res"},{"issue":"Pt 6","key":"2023060100310404900_awac473-B11","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1042\/bst0300963","article-title":"Stress granules: Sites of mRNA triage that regulate mRNA stability and translatability","volume":"30","author":"Kedersha","year":"2002","journal-title":"Biochem Soc Trans"},{"key":"2023060100310404900_awac473-B12","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/s41419-021-03873-8","article-title":"Stress granules, RNA-binding proteins and polyglutamine diseases: Too much aggregation?","volume":"12","author":"Marcelo","year":"2021","journal-title":"Cell Death Dis"},{"key":"2023060100310404900_awac473-B13","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1038\/s41467-018-05647-x","article-title":"Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration","volume":"9","author":"Sahoo","year":"2018","journal-title":"Nat Commun"},{"key":"2023060100310404900_awac473-B14","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1083\/jcb.200212128","article-title":"The RasGAP-associated endoribonuclease G3BP assembles stress granules","volume":"160","author":"Tourri\u00e8re","year":"2003","journal-title":"J Cell Biol"},{"key":"2023060100310404900_awac473-B15","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.1128\/MCB.18.7.3956","article-title":"A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: A potential link between signal transduction and RNA stability","volume":"18","author":"Gallouzi","year":"1998","journal-title":"Mol Cell Biol"},{"key":"2023060100310404900_awac473-B16","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.bbamcr.2018.09.001","article-title":"Rasputin a decade on and more promiscuous than ever? A review of G3BPs","volume":"1866","author":"Alam","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"2023060100310404900_awac473-B17","doi-asserted-by":"crossref","first-page":"7747","DOI":"10.1128\/MCB.21.22.7747-7760.2001","article-title":"RasGAP-associated endoribonuclease G3BP: Selective RNA degradation and phosphorylation-dependent localization","volume":"21","author":"Tourri\u00e8re","year":"2001","journal-title":"Mol Cell Biol"},{"key":"2023060100310404900_awac473-B18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/jnc.13768","article-title":"Preferential binding of a stable G3BP ribonucleoprotein complex to intron-retaining transcripts in mouse brain and modulation of their expression in the cerebellum","volume":"139","author":"Martin","year":"2016","journal-title":"J Neurochem"},{"key":"2023060100310404900_awac473-B19","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/1476-4598-12-156","article-title":"Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells","volume":"12","author":"Winslow","year":"2013","journal-title":"Mol Cancer"},{"key":"2023060100310404900_awac473-B20","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1083\/jcb.201801214","article-title":"Phosphorylation of G3BP1-S149 does not influence stress granule assembly","volume":"218","author":"Panas","year":"2019","journal-title":"J Cell Biol"},{"key":"2023060100310404900_awac473-B21","doi-asserted-by":"crossref","first-page":"9310","DOI":"10.1073\/pnas.152101299","article-title":"Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis","volume":"99","author":"Chai","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023060100310404900_awac473-B22","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/hmg\/ddg175","article-title":"Expansion of the polyQ repeat in ataxin-2 alters its Golgi localization, disrupts the Golgi complex and causes cell death","volume":"12","author":"Huynh","year":"2003","journal-title":"Hum Mol Genet"},{"key":"2023060100310404900_awac473-B23","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13104-020-05053-x","article-title":"The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington\u2019s disease","volume":"13","author":"N\u00f3brega","year":"2020","journal-title":"BMC Res Notes"},{"key":"2023060100310404900_awac473-B24","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s12311-012-0432-0","article-title":"Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology","volume":"12","author":"N\u00f3brega","year":"2013","journal-title":"Cerebellum"},{"key":"2023060100310404900_awac473-B25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12031-012-9930-2","article-title":"Generation of human-induced pluripotent stem cells to model spinocerebellar ataxia type 2 in vitro","volume":"51","author":"Xia","year":"2013","journal-title":"J Mol Neurosci"},{"key":"2023060100310404900_awac473-B26","doi-asserted-by":"crossref","DOI":"10.1038\/srep28220","article-title":"Fibroblasts of Machado Joseph disease patients reveal autophagy impairment","volume":"6","author":"Onofre","year":"2016","journal-title":"Sci Rep"},{"key":"2023060100310404900_awac473-B27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nmeth.1314","article-title":"SUnSET, a nonradioactive method to monitor protein synthesis","volume":"6","author":"Schmidt","year":"2009","journal-title":"Nat Methods"},{"key":"2023060100310404900_awac473-B28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/10430340050016256","article-title":"Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson\u2019s disease","volume":"11","author":"D\u00e9glon","year":"2000","journal-title":"Hum Gene Ther"},{"key":"2023060100310404900_awac473-B29","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1523\/JNEUROSCI.22-09-03473.2002","article-title":"Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length","volume":"22","author":"De","year":"2002","journal-title":"J Neurosci"},{"issue":"Pt 8","key":"2023060100310404900_awac473-B30","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1093\/brain\/aws177","article-title":"Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease","volume":"135","author":"Sim\u00f5es","year":"2012","journal-title":"Brain"},{"key":"2023060100310404900_awac473-B31","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1242\/jcs.115.16.3227","article-title":"Stressful initiations","volume":"115","author":"Anderson","year":"2002","journal-title":"J Cell Sci"},{"key":"2023060100310404900_awac473-B32","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbadis.2016.12.022","article-title":"Cytoplasmic stress granules\u202f: Dynamic modulators of cell signaling and disease","volume":"1863","author":"Mahboubi","year":"2017","journal-title":"BBA Mol Basis Dis"},{"key":"2023060100310404900_awac473-B33","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1091\/mbc.e06-12-1120","article-title":"Ataxin-2 interacts with the DEAD\/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules","volume":"18","author":"Nonhoff","year":"2007","journal-title":"Mol Biol Cell"},{"key":"2023060100310404900_awac473-B34","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1083\/jcb.147.7.1431","article-title":"RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules","volume":"147","author":"Kedersha","year":"1999","journal-title":"J Cell Biol"},{"key":"2023060100310404900_awac473-B35","first-page":"1","article-title":"Principles and properties of stress granules","volume":"xx","author":"Protter","year":"2016","journal-title":"Trends Cell Biol"},{"key":"2023060100310404900_awac473-B36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41590-018-0262-4","article-title":"G3BP1 promotes DNA binding and activation of cGAS","volume":"20","author":"Liu","year":"2019","journal-title":"Nat Immunol"},{"key":"2023060100310404900_awac473-B37","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.1074\/jbc.RA118.005868","article-title":"The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-\u03b2 response","volume":"294","author":"Kim","year":"2019","journal-title":"J Biol Chem"},{"key":"2023060100310404900_awac473-B38","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nrm2178","article-title":"RNA-binding proteins: Modular design for efficient function","volume":"8","author":"Lunde","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2023060100310404900_awac473-B39","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0968-0004(00)89024-6","article-title":"The RNP domain: A sequence-specific RNA-binding domain involved in processing and transport of RNA","volume":"20","author":"Nagai","year":"1995","journal-title":"Trends Biochem Sci"},{"key":"2023060100310404900_awac473-B40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0080947","article-title":"Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG nup repeat specificity","volume":"8","author":"Vognsen","year":"2013","journal-title":"PLoS ONE"},{"key":"2023060100310404900_awac473-B41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/jcb.1277","article-title":"Characterization of G3BPs: Tissue specific expression, chromosomal localisation and rasGAP120 binding studies","volume":"84","author":"Kennedy","year":"2002","journal-title":"J Cell Biochem"},{"key":"2023060100310404900_awac473-B42","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1093\/hmg\/ddx191","article-title":"Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2","volume":"26","author":"Pflieger","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2023060100310404900_awac473-B43","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1093\/brain\/awv298","article-title":"Re-establishing ataxin-2 downregulates translation of mutant ataxin-3 and alleviates Machado-Joseph disease","volume":"138","author":"N\u00f3brega","year":"2015","journal-title":"Brain"},{"key":"2023060100310404900_awac473-B44","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1093\/hmg\/ddn106","article-title":"Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease","volume":"17","author":"Alves","year":"2008","journal-title":"Hum Mol Genet"},{"key":"2023060100310404900_awac473-B45","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/s41419-021-04404-1","article-title":"Autophagy in spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy","volume":"12","author":"Marcelo","year":"2021","journal-title":"Cell Death Dis"},{"key":"2023060100310404900_awac473-B46","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s004010050989","article-title":"Spinocerebellar ataxia 2 (SCA2): Morphometric analyses in 11 autopsies","volume":"97","author":"Estrada","year":"1999","journal-title":"Acta Neuropathol"},{"key":"2023060100310404900_awac473-B47","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0896-6273(00)80943-5","article-title":"Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3","volume":"19","author":"Paulson","year":"1997","journal-title":"Neuron"},{"key":"2023060100310404900_awac473-B48","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s12035-012-8315-4","article-title":"Mouse models of polyglutamine diseases: Review and data table. Part I","volume":"46","author":"Figiel","year":"2012","journal-title":"Mol Neurobiol"},{"key":"2023060100310404900_awac473-B49","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/embor.2008.31","article-title":"Lentivector-mediated rescue from cerebellar ataxia in a mouse model of spinocerebellar ataxia","volume":"9","author":"Torashima","year":"2008","journal-title":"EMBO Rep"},{"key":"2023060100310404900_awac473-B50","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0052396","article-title":"Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice","volume":"8","author":"N\u00f3brega","year":"2013","journal-title":"PLoS ONE"},{"key":"2023060100310404900_awac473-B51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainres.2008.12.014","article-title":"Characterization of mutant mice that express polyglutamine in cerebellar Purkinje cells","volume":"1255","author":"Oue","year":"2009","journal-title":"Brain Res"},{"key":"2023060100310404900_awac473-B52","doi-asserted-by":"crossref","DOI":"10.4155\/fso.15.42","article-title":"Cellular stress responses in protein misfolding diseases","volume":"1","author":"Duennwald","year":"2015","journal-title":"Future Sci OA"},{"key":"2023060100310404900_awac473-B53","doi-asserted-by":"crossref","first-page":"15810","DOI":"10.1074\/jbc.RA120.013835","article-title":"Direct evidence that ataxin-2 is a translational activator mediating cytoplasmic polyadenylation","volume":"295","author":"Inagaki","year":"2020","journal-title":"J Biol Chem"},{"key":"2023060100310404900_awac473-B54","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbadis.2016.05.017","article-title":"Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K\/mTOR and is induced by starvation","volume":"1862","author":"Lastres-Becker","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"2023060100310404900_awac473-B55","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.tem.2016.12.006","article-title":"Unraveling the role of ataxin-2 in metabolism","volume":"28","author":"Carmo-silva","year":"2017","journal-title":"Trends in Endocrinol Metab"},{"key":"2023060100310404900_awac473-B56","article-title":"Between interactions and aggregates: The PolyQ balance","volume":"13","author":"Mier","year":"2021","journal-title":"Genome Biol Evol"},{"key":"2023060100310404900_awac473-B57","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2020.00489","article-title":"The mechanisms of nuclear proteotoxicity in polyglutamine spinocerebellar ataxias","volume":"14","author":"Lee","year":"2020","journal-title":"Front Neurosci"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awac473\/49467983\/awac473.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/6\/2346\/50460385\/awac473.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/6\/2346\/50460385\/awac473.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:36:09Z","timestamp":1685579769000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/146\/6\/2346\/6895270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":57,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,12,13]]},"published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awac473","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6]]},"published":{"date-parts":[[2022,12,13]]}}}