A5007655910- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- RNA regulation and disease
- Neurological disorders and treatments
- DNA Repair Mechanisms
- 3D Printing in Biomedical Research
- Physiological and biochemical adaptations
- Cancer Research and Treatment
- Neuroscience and Neural Engineering
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Virus-based gene therapy research
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Tryptophan and brain disorders
- Connexins and lens biology
- Psychedelics and Drug Studies
- Genetics, Aging, and Longevity in Model Organisms
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2014-2025
Duke University
2024
Duke University Hospital
2024
Duke Medical Center
2024
Jagiellonian University
2024
Polish Academy of Sciences
2023
Institut de génétique et de biologie moléculaire et cellulaire
2022
Inserm
2022
Université de Strasbourg
2022
Centre National de la Recherche Scientifique
2022
In the brain, glutamatergic neurotransmission is terminated predominantly by rapid uptake of synaptically released glutamate into astrocytes through Na(+)-dependent transporters GLT-1 and GLAST its subsequent conversion glutamine enzyme synthetase (GS). To date, several factors have been identified that rapidly alter glial post-translational modification transporters. The only condition known to affect expression GS coculturing glia with neurons. We now demonstrate neurons regulate turnover...
Steroids that activate glucocorticoid receptors (GRs) and mineralocorticoid have important regulatory effects on neural development, plasticity, the body's stress response. Here, we investigated role of corticosteroids in regulating expression glial glutamate transporters transporter-1 (GLT-1) glutamate-aspartate transporter (GLAST) rat primary astrocytes. The synthetic dexamethasone provoked a marked increase GLT-1 transcription protein levels cortical astrocytes, whereas GLAST remained...
Spinocerebellar ataxia type 3 (SCA3/MJD) is a neurodegenerative disease triggered by the expansion of CAG repeats in ATXN3 gene. Here, we report generation first humanized ataxin-3 knock-in mouse model (Ki91), which provides insights into neuronal and glial pathology SCA3/MJD. First, mutant accumulated cell nuclei across Ki91 brain, showing diffused immunostaining forming intranuclear inclusions. The allele revealed contraction intergenerational transmissions. mutation also exhibited...
Huntington disease (HD) is an incurable brain disorder characterized by the late onset of motor and cognitive symptoms, even though neurons in begin to suffer dysfunction degeneration long before symptoms appear. Several molecular developmental effects HD have been identified using neural stem cells (NSCs) differentiated cells, such as astrocytes. Still, little known regarding pathogenesis pluripotent embryonic (ESCs) induced (iPSCs). Therefore, we examined putative signaling pathways...
Polyglutamine (polyQ)-encoding CAG repeat expansions represent a common disease-causing mutation responsible for several dominant spinocerebellar ataxias (SCAs). PolyQ-expanded SCA proteins are toxic cerebellar neurons, with Purkinje cells (PCs) being the most vulnerable. RNA interference (RNAi) reagents targeting transcripts expanded reduce level of various mutant in an allele-selective manner vitro and promising universal tools treating multiple CAG/polyQ SCAs. However, it remains unclear...
Huntington’s disease (HD) is a polyglutamine neurodegenerative involving pathogenesis within the striatum and cerebral cortex neurodevelopmental component, particularly in juvenile HD form (JOHD). We established fused dorsal-ventral system, imitating interaction single organoid to discover impairments at level of cell populations. found range early pathogenic phenotypes indicating that brain development affected by impaired neurogenesis. The occurred already early-stage 60-day organoids...
Huntington’s disease (HD) is a polyglutamine neurodegenerative involving pathogenesis within the striatum and cerebral cortex neurodevelopmental component, particularly in juvenile HD form (JOHD). We established fused dorsal-ventral system, imitating interaction single organoid to discover impairments at level of cell populations. found range early pathogenic phenotypes indicating that brain development affected by impaired neurogenesis. The occurred already early-stage 60-day organoids...
In polyglutamine (polyQ) diseases, including Huntington disease (HD) and spinocerebellar ataxia type 3 (SCA3), targeting the mutant CAG tract in mRNA could be a therapeutic strategy for lowering pathogenic protein. We explored viability of this vivo at level reagent design, toxicity, systemic delivery, brain regions transduction, silencing efficiency, allele preference. designed series CAG-directed short hairpin RNAs (shRNAs) based on previous A2 reagent, selective vitro. Humanized HD...
Among the many proposed therapeutic strategies for Huntington's disease (HD), allele-selective therapies are most desirable but also challenging. RNA interference (RNAi) tools that target CAG repeats selectively reduce mutant huntingtin level in cellular models of HD. The purpose this study was to test efficacy, selectivity, and safety two vector-based RNAi triggers an animal model repeat-targeting short hairpin (shRNA) artificial miRNA (amiRNA) were delivered brains YAC128 mice via...
Abstract The neuronal cell death associated with certain neurodegenerative disorders as well acute brain injuries is in part due to the reduced expression of glial glutamate transporters and subsequent accumulation toxic extracellular concentrations. Extracellular factors previously found potently stimulate transporters, GLT‐1/EAAT2 GLAST/EAAT1, astroglial cultures rat cerebral hemispheres are PACAP, TGFα, EGF. In present study, we sought determine whether similar stimulatory influences...
Spinocerebellar ataxia 3 (SCA3) is a genetic disorder resulting from the expansion of CAG repeats in ATXN3 gene. The pathogenesis SCA3 based on toxic function mutant ataxin-3 protein, but exact mechanism disease remains elusive. Various types transgenic mouse models explore different aspects pathogenesis, knock-in humanized has not yet been created. initial aim this study was to generate an model using strategy. human cDNA for containing 69 cloned patient and introduced into locus at exon 2,...
How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, ranging from emergency medicine space travel. Studying hibernation-like response in the free-living nematode Caenorhabditis elegans, we uncovered regulatory axis that enhances natural resistance of nematodes severe cold. This involves conserved transcription factors, DAF-16/FoxO and PQM-1, which jointly promote survival by upregulating FTN-1, protein related mammalian...
In Huntington disease (HD) subtle symptoms in patients may occur years or even decades prior to diagnosis. HD changes at a molecular level begin as early cells that are non-lineage committed such stem induced pluripotent (iPSCs) offering opportunity enhance the understanding of pathogenesis. addition, juvenile non-linage were previously not directly investigated detail by RNA-seq. present manuscript, we define and transcriptional alterations using 6 human iPS cell lines from two patients,...
Glutamate is the main excitatory neurotransmitter in mammalian central nervous system which at high extracellular levels leads to neuronal over-stimulation and subsequent excitotoxic cell death. Both termination of glutamatergic neurotransmission prevention neurotoxic glutamate concentrations are predominantly achieved by uptake into astroglia through high-affinity transporters, amino acid transporter-2/glutamate transporter-1 (EAAT-2/GLT-1) EAAT-1/glutamate aspartate transporter (GLAST)....
Abstract Psychedelics are new, promising candidate molecules for clinical use in psychiatric disorders such as Treatment-Resistant Depression (TRD) and Post Traumatic Stress Disorder (PTSD). They were recently also proposed supporting neural tissue repair by anti-inflammatory properties. Here we reported that two classic psychedelics, DMT psilocin, can influence microglial functions reducing the level of TLR4, p65, CD80 proteins, which markers immune response, upregulat TREM2 neuroprotective...
Abstract In the vertebrate CNS, glutamate transport predominantly occurs through transporter subtype, GLT‐1/EAAT‐2, which prevails in astrocytes. GLT‐1/EAAT‐2 expression is impaired many acute and chronic brain diseases, leading to increases extracellular subsequent excitotoxic neuronal cell death. An obvious therapeutical approach prevent glutamate‐induced damage would be targeting expression. Since so far, insights into mechanisms modulating mostly originated from work with rat astrocytes,...
Spinocerebellar ataxia type 3 (SCA3/MJD) is a polyQ neurodegenerative disease where the presymptomatic phase of pathogenesis unknown. Therefore, we investigated molecular network transcriptomic and proteomic triggers in young SCA3/MJD brain from Ki91 knock-in mouse. We found that transcriptional dysregulations resulting mutant ataxin-3 are not occurring mice, while old mice also postmitotic patient SCA3 neurons demonstrate late changes. Unlike lack early mRNA changes, have identified...