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Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails ...
Garcia, Daniela Raquel Cunha; Fernandes, Daniela Monteiro; Correia, Joana Sofia; Carvalho, Andreia Alexandra NevesSpinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common p...
Assessment of the gastrointestinal fate of bacterial nanocellulose and its toxi...
Rodrigues, Ana Cristina Costa; Costa, Liliana Marisa Barros; Silva-Carvalho, Ricardo; Mota, Renato; Duarte-Silva, SaraBacterial nanocellulose (BNC), a nanofibrillar polysaccharide produced by certain acetic acid bacteria, may be used in food, pharma and many other applications. As with other nanoscale celluloses, the oral toxicology of BNC is still controversial. Therefore, we aimed to assess whether BNC is absorbed at the intestine following administration in Wistar rats. This is, to our knowledge, the first attempt to track ...
Learning the biochemical basis of axonal guidance: using Caenorhabditis elegans...
Castro, Andreia Cristiana Teixeira; Sousa, João Carlos; Vieira, Cármen Maria Leal; Pereira-Sousa, Joana; Vilasboas-Campos, Daniela; Marques, FernandaAim: Experimental models are a powerful aid in visualizing molecular phenomena. This work reports how the worm <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) can be effectively explored for students to learn how molecular cues dramatically condition axonal guidance and define nervous system structure and behavior at the organism level. Summary of work: A loosely oriented observational activity preceded detai...
Aripiprazole offsets mutant ATXN3-induced motor dysfunction by targeting dopami...
Jalles, Ana; Vieira, Cármen Maria Leal; Pereira-Sousa, Joana; Campos, Daniela Vilasboas; Mota, Ana Francisca; Vasconcelos, SaraThe atypical antipsychotic aripiprazole is a Food and Drug Administration-approved drug for the treatment of psychotic, mood, and other psychiatric disorders. Previous drug discovery efforts pinpointed aripiprazole as an effective suppressor of Machado–Joseph disease (MJD) pathogenesis, as its administration resulted in a reduced abundance and aggregation of mutant Ataxin-3 (ATXN3) proteins. Dopamine partial ag...
Profiling microglia in a mouse model of Machado-Joseph disease
Campos, Ana Bela; Silva, Sara Carina Duarte; Fernandes, B.; Neves, Sofia Pereira; Marques, Fernanda; Castro, Andreia Cristiana TeixeiraMicroglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado–Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultur...
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebel...
Correia, Joana Sofia Silva; Carvalho, Andreia Alexandra Neves; Pinheiro, Bárbara Filipa Mendes; Pires, Joel Pereira; Teixeira, Fábio Gabriel RodriguesThe low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathop...
Neurotherapeutic effect of Hyptis spp. leaf extracts in Caenorhabditis elegans ...
Vilasboas-Campos, Daniela; Costa, Marta Daniela Araújo; Castro, Andreia Cristiana Teixeira; Rios, Rejaine; Silva, Fabiano Guimarães; Bessa, CarlosHyptis suaveolens (HS), Hyptis pectinata (HP) and Hyptis marrubioides (HM) are plants used in folk medicine for treatment of several diseases. Here, we tested the in vivo antioxidant and neuroprotective potential of methanolic extracts from these plants, containing several rosmarinic acid derivatives and isoquercetin. In C. elegans, HS, HP and HM leaf extracts enhanced the antioxidant responses through the indu...
Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Mac...
Esteves, Sofia; Oliveira, Stéphanie Pereira; Silva, Sara Carina Duarte; Cunha-Garcia, Daniela; Castro, Andreia Cristiana Teixeira; Maciel, P.Spinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis. Here, we asked whether citalo...
GST-4-dependent suppression of neurodegeneration in C. elegans models of Parkin...
Paul, Franziska; Castro, Andreia Cristiana Teixeira; Costa, Marta Daniela; Lindsay, Victoria; Fiúza-Fernandes, Juliana; Goua, Marie; Bermano, GiovannaGenetic mutations and aging-associated oxidative damage underlie the onset and progression of neurodegenerative diseases, like Parkinson's disease (PD) and Machado-Joseph disease (MJD). Natural products derived from plants have been regarded as important sources of novel bioactive compounds to counteract neurodegeneration. Here, we tested the neuroprotective effect of an ethanolic extract of rapeseed pomace (RS...
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 ...