Project/scholarship details
- Project/scholarship ID
60412
- Reference
POCI/SAU-MMO/60412/2004
- FundRef URI
- Funder
FCT - Fundação para a Ciência e a Tecnologia, I.P.
- Funder's country
Portugal
- Funding program
POCI
- Funding amount
77,900.00 €
- Start date
2005-07-01
- End date
2008-06-30
Documents
Functional genomics and biochemical characterization of the C. elegans ortholog...
Rodrigues, Ana João; Coppola, Giovanni; Santos, Cláudia; Costa, Maria do Carmo; Ailion, Michael; Sequeiros, Jorge; Geschwind, Daniel H.; Maciel, P.Machado-Joseph disease (MJD) is the most common dominant spinocerebellar ataxia. MJD is caused by a CAG trinucleotide expansion in the ATXN3 gene, which encodes a protein named ataxin-3. Ataxin-3 has been proposed to act as a deubiquitinating enzyme in the ubiquitin-proteasome pathway and to be involved in transcriptional repression; nevertheless, its precise biological function(s) remains unknown. To gain furt...
ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans
Rodrigues, Ana João; Carvalho, Andreia Alexandra Neves; Ferro, Anabela; Rokka, Anne; Corthals, Garry; Logarinho, Elsa; Maciel, P.Ataxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified ...
Absence of ataxin-3 leads to cytoskeletal disorganization and increased cell death
Rodrigues, Ana João; Costa, Maria do Carmo; Silva, Teresa L; Ferreira, Daniela; Bajanca, Fernanda; Santos, Elsa Clara Carvalho Logarinho; Maciel, P.Ataxin-3 (ATXN3) is a widely expressed protein that binds to ubiquitylated proteins, has deubiquitylating activity in vitro and is thought to modulate substrate degradation through the ubiquitin-proteasome pathway. Expansion of a polyglutamine tract in ATXN3 causes Machado-Joseph disease, a late-onset neurodegenerative disorder characterized by ubiquitin-positive aggregate formation and specific neuronal death....
Absence of ataxin-3 leads to enhanced stress response in C. elegans
Rodrigues, Ana João; Carvalho, Andreia Neves; Castro, Andreia Cristiana Teixeira de; Rokka, Anne; Corthals, Gary; Logarinho, Elsa; Maciel, P.Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitinproteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never...
Lithium chloride therapy fails to improve motor function in a transgenic mouse ...
Silva, Sara Duarte; Carvalho, Andreia Neves; Cunha, Carina Soares; Castro, Andreia Cristiana Teixeira de; Oliveira, Pedro; Fernandes, Anabela SilvaThe accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed...
Chronic treatment with 17-DMAG improves balance and coordination in a new mouse...
Fernandes, Anabela Silva; Silva, Sara Duarte; Carvalho, Andreia Neves; Amorim, Marina; Cunha, Carina Soares; Oliveira, Pedro; Thirstrup, KennethMachado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in k...
Combined therapy with m-TOR-dependent and -independent autophagy inducers cause...
Silva, Sara Carina Duarte; Fernandes, Anabela Silva; Carvalho, Andreia Alexandra Neves; Cunha, Carina Isabel Soares; Castro, Andreia Cristiana TeixeiraA major pathological hallmark in several neurodegenerative disorders, like polyglutamine disorders (polyQ), including Machado-Joseph disease (MJD), is the formation of protein aggregates. MJD is caused by a CAG repeat expansion in the ATXN3 gene, resulting in an abnormal protein, which is prone to misfolding and forms cytoplasmic and nuclear aggregates within neurons, ultimately inducing neurodegeneration. Trea...
Report
Embed
<script type="text/javascript">
<!--
document.write('<div id="rcaap-widget"></div>');
document.write('<script type="text/javascript" src="https://www.rcaap.pt/snippet?resource=documents&project=FCT%2FPOCI%2F60412&fields=id,titles,creators,issueDate,link,descriptions"></script>');
-->
</script>