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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...
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...
An image processing application for quantification of protein ag-gregates in Ca...
Castro, Andreia Cristiana Teixeira de; Dias, Nuno; Rodrigues, Pedro L.; Oliveira, João F.; Rodrigues, Nuno F.; Maciel, P.; Vilaça, João L.Protein aggregation became a widely accepted marker of many polyQ disorders, including Machado-Joseph disease (MJD), and is often used as readout for disease progression and development of therapeutic strategies. The lack of good platforms to rapidly quantify protein aggregates in a wide range of disease animal models prompted us to generate a novel image processing application that automatically identifies and...
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...
Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the ...
Castro, Andreia Cristiana Teixeira de; Ailion, Michael; Jalles, Ana; Brignull, Heather; Vilaça, João L.; Dias, N. S.; Rodrigues, Pedro L.The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado–Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependen...