Andreia Teixeira-Castro

Andreia Teixeira-Castro
University of Minho · Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho

PhD

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48
Publications
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705
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Publications

Publications (48)
Article
Full-text available
Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder (ND). While most research in NDs has been following a neuron-centric point of view, microglia are now recognized as crucial in the brain. Previous work revealed alterations that point to an increased activation state...
Article
Full-text available
The 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 aggr...
Article
Full-text available
Microglia 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. Thi...
Preprint
Full-text available
Background Bacterial cellulose (BC) is a nanofibrillar polysaccharide produced by certain acetic acid bacteria. BC may be used in food, pharma and many other applications. However, detailed studies of the oral toxicology of BC are limited. Controversial data is published regarding this topic, specially when it comes to answering the question on whe...
Article
Full-text available
The 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 de...
Article
Full-text available
Diseases of neurodevelopment mostly exhibit neurological and psychiatric symptoms that go from very mild to extremely severe. While the etiology of most cases of neurodevelopmental disease is still unknown, the discovery of underlying genetic causes is rapidly increasing, with hundreds of genes being currently implicated as disease-causing. Here, w...
Article
Background aims The capacity of the secretome from bone marrow-derived mesenchymal stem cells (BMSCs) to prevent dopaminergic neuron degeneration caused by overexpression of alpha-synuclein (α-syn) was explored using two Caenorhabditis elegans models of Parkinson's disease (PD). Methods First, a more predictive model of PD that overexpresses α-syn...
Article
Full-text available
Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder that affects movement coordination leading to a premature death. Despite several efforts, no disease-modifying treatment is yet available for this disease. Previous studies pinpointed the modulation of serotonergic signaling, through pha...
Article
Full-text available
Here, we present the data on the biological effects of Hyptis spp. and Lycium spp. plant extracts in Caenorhabditis elegans (C. elegans) models of neurodegenerative diseases, which is related to the work presented in the article “Neurotherapeutic effect of Hyptis spp. leaf extracts in C. elegans models of tauopathy and polyglutamine disease: role o...
Article
Hyptis 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 l...
Article
Introduction: Six of the most frequent dominantly inherited spinocerebellar ataxias (SCAs) worldwide - SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 - are caused by an expansion of a polyglutamine (polyQ) tract in the corresponding proteins. While the identification of the causative mutation has advanced knowledge on the pathogenesis of polyQ SCAs, effe...
Article
Full-text available
The connectome of Caenorhabditis elegans has been extensively studied and fully mapped, allowing researchers to more confidently conclude on the impact of any change in neuronal circuits based on behavioral data. One of the more complex sensorimotor circuits in nematodes is the one that regulates the integration of feeding status with the subsequen...
Chapter
Animal models have been extensively used to study the complex physiology and pathophysiology of human diseases. They are valuable for understanding biological phenomena, to understand disease development and progression, and for testing novel therapeutic strategies. The selection of the most adequate species for an animal model can be challenging f...
Article
Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease (MJD), is a neurodegenerative disorder caused by a polyglutamine expansion in the ATXN3 gene. In spite of the identification of a clear monogenic cause 25 years ago, the pathological process still puzzles researchers, impairing prospects for an effective therapy. Here, we pr...
Article
Full-text available
Genetic 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 neuro...
Article
Full-text available
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 mut...
Article
Full-text available
Machado-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...
Article
Background and Objective: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine‐enriched diet would be beneficial for a mouse model of spinocerebellar ataxia ty...
Article
Full-text available
Phospholipase D (PLD) is a key player in the modulation of multiple aspects of cell physiology and has been proposed as a therapeutic target for Alzheimer's disease (AD). Here, we characterize a PLD mutant, pld-1, using the Caenorhabditis elegans animal model. We show that pld-1 animals present decreased phosphatidic acid levels, that PLD is the on...
Article
Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implication...
Article
For a number of years there has been intense interest in phytochemicals due to their potential health benefits. One readily available and rich source of phytochemicals is Rapeseed pomace (RSP), a waste product obtained after edible oil production from Brassica napus. In this work, we analysed the ubiquitous secondary metabolites in RSP (harvest 201...
Article
Full-text available
The study of C. elegans has led to ground-breaking discoveries in gene-function, neuronal circuits, and physiological responses. Subtle behavioral phenotypes, however, are often difficult to measure reproducibly. We have developed an experimental and computational infrastructure to simultaneously record and analyze the physical characteristics, mov...
Article
A 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 aggreg...
Article
Full-text available
Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and...
Article
Full-text available
Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen...
Article
Full-text available
The 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 neuro...
Article
Full-text available
Machado-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 intra...
Article
Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)-based approaches have been investigated for repairing this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility...
Article
In the last years, it has become increasingly clear that neurodegenerative diseases involve protein aggregation, a process often used as disease progression readout and to develop therapeutic strategies. This work presents an image processing tool to automatic segment, classify and quantify these aggregates and the whole 3D body of the nematode Cae...
Article
Full-text available
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-neur...
Data
Full-text available
Primers used in this study. (PDF)
Data
Full-text available
DAF-16 targets sod-3 and mtl-1 are activated differentially in atx-3 mutants both at 20°C (A) and 25°C (B). At 20°C, sod-3 is up-regulated 90 minutes after heat shock while mtl-1 is up-regulated 15 minutes after the stress. At 25°C, sod-3 is up-regulated in all time points analyzed in atx-3 mutants while mtl-1 expression is increased starting at 15...
Data
Full-text available
Lifespan results depicted in Figure 1 . (PDF)
Data
Proteomic results from LC-ESI-MS/MS analysis of two ataxin-3 knockout strains in a basal condition and after heat shock. (XLS)
Data
Lifespan results depicted in Figure 7 . (PDF)
Article
Full-text available
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 ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal...
Chapter
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 nove...
Article
Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 gene (MECP2). Several neural systems are affected in Rett, resulting in an autonomic dysfunction, a movement disorder with characteristic loss of locomotor abilities and profound cognitive impairments. A deregulation of monoamines has been detecte...
Article
Machado-Joseph disease (MJD/SCA3) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG tract in the coding portion of the ATXN3 gene. The presence of ubiquitin-positive aggregates of the defective protein in affected neurons is characteristic of this and most of the polyglutamine disorders. Recently, the accumulation...
Article
Full-text available
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterised by chorea, cognitive impairment, dementia and personality changes, caused by the expansion of a CAG repeat in the HD gene. Often, patients with a similar clinical presentation do not carry expansions of the CAG repeat in this gene [Huntington disease-like (HDL...
Article
Full-text available
Understanding the basis for neuronal subtype-specific protein aggregation is of central importance for several human neurodegenerative diseases, including Machado-Joseph disease. In this study, we developed a novel Ataxin-3 (ATXN3) pathogenesis model in Caenorhabditis elegans and examined the aggregation profile of human ATXN3 by performing FRAP a...

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Projects (4)
Project
Determine the molecular effects of SSRI treatment in proteotoxicity, exploring the modulation of proteostasis networks by serotonin signaling pathway in neurons, as a therapeutic strategy for MJD and perhaps other neurodegenerative disorders.
Project
To understand the mechanism underlying this genetically defined neurodegenerative disorder and to develop therapeutic approaches to counteract it.
Project
Exploring the role of antioxidant gene pathways in a rapeseed pomace extract rescue of neurodegenerative disease phenotypes in C elegans disease models. Working in collaboration with the Maciel lab at the ICVS, Universidade do Minho.