A5034423723- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Metabolism and Genetic Disorders
- Lysosomal Storage Disorders Research
- Muscle Physiology and Disorders
- Amyotrophic Lateral Sclerosis Research
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Race, Genetics, and Society
- RNA modifications and cancer
- Cellular transport and secretion
- Genetic factors in colorectal cancer
- Genetics, Bioinformatics, and Biomedical Research
- Cancer, Lipids, and Metabolism
- Extracellular vesicles in disease
- Hormonal Regulation and Hypertension
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- RNA regulation and disease
- Folate and B Vitamins Research
- Pregnancy and preeclampsia studies
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2016-2025
Universidade do Porto
2014-2024
Universidade dos Açores
2015-2024
Max Delbrück Center
2023
Charité - Universitätsmedizin Berlin
2023
Faculdade de Ciências Médicas da Santa Casa de São Paulo
2021
Hospital Universitario de Canarias
2010
The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They caused by expanded CAG tracts, encoding glutamine, in different genes. Longer repeat tracts associated with earlier ages at onset, but this does not account for all of difference, existence additional genetic modifying factors has been suggested these A recent genome-wide association study (GWAS) HD found between age...
Article8 June 2020Open Access Source DataTransparent process Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage humans mice Carlo Wilke orcid.org/0000-0002-7250-8597 Hertie Institute for Clinical Brain Research (HIH), Center of Neurology, University Tübingen, Germany German Neurodegenerative Diseases (DZNE), Search more papers by this author Eva Haas Medical Genetics Applied Genomics, Centre Rare Diseases, Kathrin Reetz Department RWTH Aachen...
Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures.To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) fluid SCA3, ATXN3 mutation carriers (n = 143) controls 172) were clinically assessed, the plasma concentrations of four proteins analysed on Simoa HD-1 platform. Eleven carrier cerebrospinal samples t-tau phosphorylated (p-tau181 )....
Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy models. Here, we pinpointed tauroursodeoxycholic acid (TUDCA) as efficient therapeutic, improving motor and neuropathological phenotype of SCA3 nematode mouse Surprisingly, transcriptomic functional vivo data...
Abstract Background Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited adult-onset disease. We aimed to describe longitudinal changes in clinical and biological findings identify predictors for progression. Methods used data from participants enrolled the ESMI cohort collected between Nov 09, 2016 July 18, 2023. The freeze included 14 sites five European countries United States. assessed with Scale Assessment Rating of Ataxia (SARA). measured disease-specific mutant...
An abundance of select transcripts and proteins has been found to be dysregulated in blood samples Machado-Joseph disease (MJD) carriers. Here, we aimed to: (1) identify transcriptional changes as potential biomarkers MJD; (2) correlate levels differentially expressed with MJD carriers features; (3) evaluate whether the identified differential patients is preserved brains. We used unbiased RNA microarray quantitative polymerase chain reaction assess transcript brain samples, western blot...
Background: Spinocerebellar ataxia type 3 (SCA3) is one of the most common dominantly inherited worldwide. Despite research advances, no approved disease-modifying treatment exists, and management focuses on symptom alleviation functional capacity maximization. Symptomatic guidelines are scarce, leaving decisions to physicians' discretion. The lack studies SCA3 hinders therapy standardization. This study investigated medication usage patterns among mutation carriers controls recruited by...
<b><i>Background:</i></b> Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia caused by a CAG tract expansions in the <i>ATXN3</i> gene. Patterns of mitochondrial damage associated with pathological findings brain tissues could provide molecular biomarkers this disorder. <b><i>Objective:</i></b> The potential DNA (mtDNA) as biomarker MJD progression was investigated using transgenic mouse model....
Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by CAG repeat expansion in the ataxin-3 gene. Although no curative therapy yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are critical importance as pharmacodynamic particularly target engagement markers.We aimed at developing an ultrasensitive...
Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of development targeted therapies, knowledge early biomarker changes needed. We analyzed cross-sectional data 292 spinocerebellar mutation carriers. Blood concentrations mutant ATXN3 were high before and after onset, whereas neurofilament light deviated from normal 13.3 years onset. Pons cerebellar white matter volumes decreased 2.2 0.6 propose a staging model that includes stage...
In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the length of CAG repeat expansions in ATXN3 shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on expansion was developed European carriers. We tested this SCA3/MJD carriers from distinct origins and population-specific models to predict AO.This parametric survival modelling study.The (EF) 739 independent South Brazil, Taiwan Portuguese Azorean islands, it largely underestimated...
Transcriptional dysregulation has been described in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant caused by a polyglutamine expansion the ataxin-3 protein. As is ubiquitously expressed, transcriptional alterations blood may reflect early changes that start before clinical onset and might serve as peripheral biomarkers research settings. Our goal was to describe enriched pathways report dysregulated genes, which can track onset, severity or progression...
Machado-Joseph disease (MJD), also named spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant worldwide. Although nystagmus one of frequently reported ocular alterations in MJD patients its behaviour during course disease, namely early stages, has only recently started to be investigated. The main goal this work was characterize frequency symptomatic and presymptomatic carriers mutation, investigate usefulness as an indicator disease. We conducted observational study...
Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which caused by a CAG repeat expansion in the coding region ATXN3 gene. This presents clinical heterogeneity, cannot be completely explained size tract. MJD extrapyramidal motor signs, namely Parkinsonism, more frequently than other subtypes cerebellar ataxias. Although Parkinsonism seems to segregate within families, only few patients develop parkinsonian...
ABSTRACT Background Machado‐Joseph disease (or spinocerebellar ataxia type 3) is a late‐onset polyglutamine neurodegenerative disorder caused by mutation in the ATXN3 gene, which encodes for ubiquitously expressed protein ataxin‐3. Previous studies on cell and animal models have suggested that mutated ataxin‐3 involved transcriptional dysregulation. Starting with whole‐transcriptome profiling of peripheral blood samples from patients controls, we aimed to confirm abnormal expression profiles...
Machado-Joseph disease (MJD) is a dominant neurodegenerative caused by an expanded CAG repeat in the ATXN3 gene encoding ataxin-3 protein. Several cellular processes, including transcription and apoptosis, are disrupted MJD. To gain further insights into extent of dysregulation mitochondrial apoptosis MJD to evaluate if expression alterations specific genes/proteins can be used as transcriptional biomarkers disease, levels BCL2, BAX TP53 BCL2/BAX ratio (an indicator susceptibility apoptosis)...
Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is a heritable proteinopathy disorder, whose causative gene, ATXN3, undergoes alternative splicing. Ataxin-3 protein isoforms differ in their toxicity, suggesting that certain ATXN3 splice variants may be crucial driving the selective toxicity SCA3. Using RNA-seq datasets we identified and determined abundance of annotated transcripts blood (n = 60) cerebellum 12) SCA3 subjects controls. The reference transcript (ATXN3–251),...
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of development targeted therapies for SCA3, precise knowledge stage-dependent fluid and MRI biomarker changes needed. We analyzed cross-sectional data 292 SCA3 mutation carriers including 57 pre-ataxic individuals, 108 healthy controls from European Disease Initiative (ESMI) cohort. Blood concentrations mutant ATXN3 neurofilament light (NfL) were determined, volumes pons,...
The present study on long-term outcome of presymptomatic testing for Machado-Joseph disease (MJD) aimed to evaluate the psychological well-being and familial satisfaction subjects that 5 years prior received an unfavorable result in predictive (PT). included 47 testees Azorean origin (23 from island Flores 24 S. Miguel) completed fourth evaluation session MJD protocol, undertook a neurological examination at moment participation study. Nearly 50% were symptomatic time Psychological...