A5072044779- Alzheimer's disease research and treatments
- Fungal and yeast genetics research
- Parkinson's Disease Mechanisms and Treatments
- Biofuel production and bioconversion
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Protein Kinase Regulation and GTPase Signaling
- Plant Gene Expression Analysis
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Biotechnology and Related Fields
- Hereditary Neurological Disorders
- Biochemical and biochemical processes
- Fungal Biology and Applications
- RNA regulation and disease
- Organizational Management and Leadership
- Click Chemistry and Applications
- Neurology and Historical Studies
KU Leuven
2001-2021
University of Vienna
2000-2001
Vienna Biocenter
2000-2001
Vrije Universiteit Amsterdam
1993-1997
Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification class compounds called ReS19-T, which are able to restore homeostasis in cell-based models tau pathology. Aberrant accumulation leads uncontrolled activation store-operated channels (SOCCs) by remodeling septin filaments at cell cortex. Binding ReS19-T septins restores filament assembly state and restrains entry through SOCCs. In amyloid-β tau-driven mouse disease,...
Summary In the yeast Saccharomyces cerevisiae , PKA and Sch9 exert similar physiological roles in response to nutrient availability. However, their functional redundancy complicates distinguish properly target genes for both kinases. this article, we analysed different phenotypic read‐outs. The data unequivocally showed that kinases act through separate signalling cascades. addition, genome‐wide expression analysis under conditions with strains which either and/or was specifically affected,...
In this work, uniform manifold approximation and projection (UMAP) is applied for nonlinear dimensionality reduction visualization of mass spectrometry imaging (MSI) data. We evaluate the performance UMAP algorithm on MSI data sets acquired in mouse pancreas human lymphoma samples compare it to those principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), Barnes–Hut (BH) t-SNE. Furthermore, we different distance metrics t-SNE propose use spatial...
A yeast model was generated to study the mechanisms and phenotypical repercussions of expression α‐synuclein as well coexpression protein tau. The data show that aggregation is a nucleation–elongation process initiated at plasma membrane. Aggregation consistently enhanced by dimethyl sulfoxide, which known increase level phospholipids membranes in cells. also triggered treatment cells with ferrous ions, are oxidative stress. In addition, presented support hypothesis degradation occurs via...
In budding yeast, cAMP-dependent protein kinase (PKA) plays a central role in the nutritional control of metabolism, cell cycle, and transcription. This study shows that both regulatory subunit Bcy1p catalytic Tpk1p associated with it are predominantly localized nucleus rapidly growing cells. Activation nuclear PKA by cAMP leads to fast entry significant part into cytoplasm, while remains nuclear. contrast proliferating cells, distributed over cytoplasm cells on nonfermentable carbon source...
In Saccharomyces cerevisiae the subcellular distribution of Bcy1 is carbon source dependent. glucose-grown cells, almost exclusively nuclear, while it appears more evenly distributed between nucleus and cytoplasm in source-derepressed cells. Here we show that phosphorylation its N-terminal domain directs to cytoplasm. Biochemical fractionation revealed cytoplasmic fraction contains mostly phosphorylated Bcy1, whereas unmodified predominantly present nuclear fraction. Site-directed...
Addition of glucose or fructose to cells the yeast Saccharomyces cerevisiae grown on a nonfermentable carbon source triggers within few minutes post-translational activation trehalase, repression CTT1 (catalase) and SSA3 (Hsp70) genes, induction ribosomal protein genes RPL1, RPL25 RPS33. By using appropriate sugar kinase mutants, it was shown that rapid glucose- fructose-induced trehalase requires phosphorylation sugar. On other hand, partial RPS33 as well were observed in absence...
All ribosomal protein (rp) gene promoters from Saccharomyces cerevisiae studied so far contain either (usually two) binding sites for the global regulator Rap1p or one site another factor, Abf1p. Previous analysis of rpS33 and rpL45 suggested that apart Abf1 site, additional cis-acting elements play a part in transcription activation these genes. We designed promoter reconstruction system based on beta-glucuronidase reporter to examine role other putative promoting transcription. An isolated...
We report here that budding yeast cAMP-dependent protein kinase (cAPK) is controlled by heat stress. A rise in temperature from 30 to 37 degrees C was found result both a higher expression and an increased cytoplasmic localization of its regulatory subunit Bcy1. Both these effects required phosphorylation serines located domain. Surprisingly, classic cAPK-controlled processes were be independent Bcy1 phosphorylation, indicating modifications do not affect cAPK activity as such....
The APP[V717I] London (APP-Ld) mouse model recapitulates important pathological and clinical hallmarks of Alzheimer's disease (AD) is therefore a valuable paradigm for evaluating therapeutic candidates. Historically, both the parenchymal vascular amyloid deposits, more recently, truncated pyroglutamate-modified Abeta(3(pE)-42) species, are perceived as AD-pathology. Late stage symptoms preceded by robust deficits in orientation memory that correlate time with Abeta oligomerization...
Nutrients are major determinants of ribosomal protein (rp-) gene transcription in Saccharomyces cerevisiae . In order to investigate the molecular mechanisms underlying this nutritional control, yeast mutants that display defects glucose upshift response rp-gene were isolated. Interestingly, although growth these on glucose-containing medium was severely affected an initial increase by still observed. However, at later time points, rp-mRNA levels decreased strongly. Various other types...
Addition of glucose to yeast cells growing on less preferred carbon sources triggers profound changes in the expression levels several genes. This paper focuses signal transduction pathways leading transcriptional activation glycolysis Saccharomyces cerevisiae during transition from respiratory fermentative growth conditions. To this end, we studied regulation glycolytic genes ( PFK1 , PYK1 and PDC ), one gluconeogenic gene FBP1 ) two encoding 6‐phosphofructo‐2‐kinase isoenzymes PFK26 PFK27...
Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive impairment cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % cases induced a complex interplay between genetic environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) pesticides fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects...
Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer's disease pathology progression. Amyloid-beta together with non-genetic risk-factors of contributes to increased influx aberrant neuronal activity, which accelerates neurodegeneration feed-forward fashion. As such, identifying new targets drugs modulate excessive signalling hyperactivity, without overly suppressing them, has promising therapeutic potential.Here we show, using biochemical, electrophysiological,...
Valosin-containing protein (VCP) is a ubiquitously expressed type II AAA+ ATPase protein, implicated in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This study aimed to explore the impact of disease-causing VCPR191Q/wt mutation on mitochondrial function using CRISPR/Cas9-engineered neuroblastoma cell line. Mitochondria these cells are enlarged, with depolarized membrane potential associated increased respiration electron transport chain activity. Our results...