4 documents found, page 1 of 1
Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Mach...
Ashraf, Naila S.; Silva, Sara Carina Duarte; Shaw, Emily D.; Maciel, P.; Paulson, Henry L.; Castro, Andreia Cristiana Teixeira; Costa, Maria do CarmoMachado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse ...
Dominant negative effect of polyglutamine expansion perturbs normal function of...
Carvalho, Andreia Alexandra Neves; Logarinho, Elsa; Freitas, Ana; Silva, Sara Duarte; Costa, Maria do Carmo; Fernandes, Anabela SilvaThe physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integr...
Valosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3
Laço, Mário N.; Cortes, Luísa; Travis, Sue M.; Paulson, Henry L.; Rego, A. CristinaAlterations in the ubiquitin-proteasome system (UPS) have been reported in several neurodegenerative disorders characterized by protein misfolding and aggregation, including the polylgutamine diseases. Machado-Joseph disease (MJD) or Spinocerebellar Ataxia type 3 is caused by a polyglutamine-encoding CAG expansion in the ATXN3 gene, which encodes a 42 kDa deubiquitinating enzyme (DUB), ataxin-3. We investigated...
Ataxin-3 plays a role in mouse myogenic differentiation through regulation of i...
Costa, Maria do Carmo; Bajanca, Fernanda; Rodrigues, Ana João; Tomé, Ricardo J.; Corthals, Gary; Ribeiro, Sandra Macedo; Paulson, Henry L.BACKGROUND: During myogenesis several transcription factors and regulators of protein synthesis and assembly are rapidly degraded by the ubiquitin-proteasome system (UPS). Given the potential role of the deubiquitinating enzyme (DUB) ataxin-3 in the UPS, and the high expression of the murine ataxin-3 homolog in muscle during embryogenesis, we sought to define its role in muscle differentiation. METHODOLOGY/PRIN...