A5047692078- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- Stress Responses and Cortisol
- Amyotrophic Lateral Sclerosis Research
- Neurological disorders and treatments
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Sleep and Wakefulness Research
- Neuropeptides and Animal Physiology
- MicroRNA in disease regulation
- Tryptophan and brain disorders
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Adenosine and Purinergic Signaling
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Hormonal Regulation and Hypertension
- Neuroendocrine regulation and behavior
- Vitamin C and Antioxidants Research
University of Coimbra
2014-2024
Hôpital Gui de Chauliac
2023
University Hospital Bonn
2023
ZB MED - Information Centre for Life Sciences
2023
Massachusetts General Hospital
2023
Max Delbrück Center
2023
Charité - Universitätsmedizin Berlin
2023
Significance Epidemiological studies show that individuals exposed to repeated stress, a major trigger of depression, increase their caffeine intake, which correlates inversely with the incidence depression. However, mechanism underlying this protective effect is unknown. We used an animal model chronic unpredictable stress (CUS) prevents maladaptive changes caused by CUS in manner mimicked selective blockade adenosine A 2A receptors (A R). enhanced R synapses, and elimination neuronal...
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...
Significance Autophagy impairment is a major hallmark of aging, and any intervention that enhances autophagy potential interest to delay aging. However, it was described the hypothalamus brain area with key role on whole-body In present study, we show an endogenous molecule produced by hypothalamus, neuropeptide Y (NPY), stimulates in rodent hypothalamus. Because both hypothalamic NPY levels decrease age, better understanding neuronal regulation may provide new putative therapeutic...
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 )....
Chromaffin cells, sympathetic neurons of the dorsal ganglia, and intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to closely related nervous system, within adult adrenal medulla subpopulation undifferentiated persists, recently, we established method isolate differentiate these bovine adrenals. However, no studies have elucidated existence human medulla. Here describe isolation, characterization, differentiation chromaffin obtained...
Extracellular vesicles (EVs) are membranous structures that protect RNAs from damage when circulating in complex biological fluids, such as plasma. extremely specific to health and disease, being powerful tools for diagnosis, treatment response monitoring, development of new therapeutic strategies several diseases. In this context, EVs potential sources disease biomarkers promising delivery vehicles. However, standardized reproducible EV isolation protocols easy implement clinical practice...
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...
Abstract Background Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for Assessment and Rating of Ataxia (SARA) sum score, but little known about contributions progression patterns individual items. Objectives To investigate temporal dynamics SARA item scores SCA3 patients evaluate if clinical demographic factors are differentially associated with evolution axial appendicular ataxia. Methods In a prospective, multinational cohort study involving 11...
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...
Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder, caused by over-repetition of the polyglutamine-codifying region in ATXN3 gene. Strategies based on suppression deleterious gene products have demonstrated promising results pre-clinical studies. Nonetheless, these strategies do not target root cause disease. In order to prevent downstream toxic pathways, our goal was develop editing-based permanently inactivate human TALENs and CRISPR-Cas9 systems...
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...
Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD) are associated hypothalamic dysfunction neuronal cell death. Additionally, the hypothalamus is a neurogenic region constitutive capacity to generate new cells of lineage, in adult rodents. The aim present work was evaluate expression feeding-related neuropeptides progenitor their differentiate functional neurons which have been described be affected by dysfunction. Our study shows...
Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of dominantly inherited ataxias worldwide and characterized by mutant ataxin-3 aggregation neuronal degeneration. There no treatment available to block or delay progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food cosmetic industry, would rescue biochemical, behavioral neuropathological features an vitro severe MJD transgenic mouse...
In the central nervous system (CNS), crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived vesicles (bdEVs). To study endogenous communication across brain and periphery, we explored Cre-mediated DNA recombination to permanently record functional uptake of bdEVs cargo over time. elucidate transfer within at physiological levels, promoted continuous secretion levels containing Cre mRNA from a localized region in situ lentiviral transduction striatum...
Abstract The establishment of robust human brain organoids to model cerebellar diseases is essential study new therapeutic strategies for cerebellum-associated disorders. Machado-Joseph disease (MJD) a hereditary neurodegenerative disease, without options able prevent the progression. In present work, control and MJD induced-pluripotent stem cells were used establish organoids. These characterized regarding development, cell type composition, MJD-associated neuropathology markers, evaluate...
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...
Little is known about the progression of health-related quality life (HRQoL) and predicting factors in spinocerebellar ataxia (SCA). Such knowledge crucial to identify modifiable promoting everyday with SCA attenuating HRQoL decline.
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),...
Abstract Background Non-motor symptoms (NMS) are a substantial burden for patients with SCA3. There limited data on their frequency, and relation disease severity activities of daily living is not clear. In addition, lifestyle may either influence or be affected by the occurrence NMS. Objective To characterize NMS in SCA3 investigate possible associations factors. Methods prospective cohort study, we performed cross-sectional analysis 227 patients, 42 pre-ataxic mutation carriers, 112...