A5080234805- Zebrafish Biomedical Research Applications
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Renal function and acid-base balance
- PI3K/AKT/mTOR signaling in cancer
- Pediatric Urology and Nephrology Studies
- Lysosomal Storage Disorders Research
- Mosquito-borne diseases and control
- Retinopathy of Prematurity Studies
- Viral Infections and Outbreaks Research
- RNA Research and Splicing
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Viral Infections and Vectors
- Neurogenesis and neuroplasticity mechanisms
- Genomics and Rare Diseases
- Skin Diseases and Diabetes
- Glycogen Storage Diseases and Myoclonus
- Escherichia coli research studies
KU Leuven
2013-2025
VIB-KU Leuven Center for Brain & Disease Research
2012-2020
Stichting Epilepsie Instellingen Nederland
2017
National Institute of Neurological Disorders and Stroke
2017
National Institutes of Health
2017
Neuroscience Institute
2017
Hokkaido University
2017
Mario Negri Institute for Pharmacological Research
2017
University of Calgary
2017
The University of Melbourne
2017
Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface lysosomes. They act in a non-redundant manner to anchor tuberous sclerosis complex (TSC) protein lysosomes suppress activation metabolic master regulator mechanistic target rapamycin (mTORC1) by amino acids insulin. Like TSC complex, G3BP1 deficiency elicits phenotypes related mTORC1...
Abstract Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher concentrations are often problematic. This raises the question whether of natural sequences can be improved. We here show an anti-correlation between number aggregation prone regions (APRs) in a sequence its solubility, suggesting mutational suppression APRs provides simple strategy increase solubility. mutations at specific positions within structure act as APR...
<h3>Objective:</h3> Voltage-gated sodium channel (Na<sub>v</sub>)–encoding genes are among early-onset epileptic encephalopathies (EOEE) targets, suggesting that other encoding Na<sub>v</sub>–binding proteins, such as fibroblast growth factor homologous factors (FHFs), may also play roles in these disorders. <h3>Methods:</h3> To identify additional for EOEE, we performed whole-exome sequencing a family quintet with 2 siblings lethal disease characterized by EOEE and cerebellar atrophy. The...
Abstract Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations ARSs have emerged as cause recessive, often complex neurological disease traits. Here we report an allelic series consisting seven novel and two previously reported biallelic variants valyl-tRNA synthetase ( VARS ) ten patients developmental encephalopathy microcephaly, associated early-onset epilepsy. In silico, vitro, yeast...
The Rift Valley fever virus (RVFV) causes haemorrhagic fever, encephalitis, and permanent blindness has been listed by the WHO as a priority pathogen. To study RVFV pathogenesis identify small-molecule antivirals, we established novel In Vivo model using zebrafish larvae. Pericardial injection of resulted in ~4 log10 viral RNA copies/larva, which was inhibited antiviral 2′-fluoro-2′-deoxycytidine. optical transparency larvae allowed detection RVFVeGFP liver sensory nervous system, including...
Abstract Epilepsy is a chronic brain disorder characterized by recurrent seizures due to abnormal, excessive and synchronous neuronal activities in the brain. It affects approximately 65 million people worldwide, one third of which are still estimated suffer from refractory seizures. Glutamic acid decarboxylase (GAD) that converts glutamate into GABA key enzyme dynamic regulation neural network excitability. Importantly, clinical evidence shows lowered GAD activity associated with several...
Development of RNA-based technologies relies on the ability to detect, manipulate, and modify RNA. Efficient, selective scalable covalent modification long RNA molecules remains a challenge. We report chemical method for 3'-end based previously unrecognized superior reactivity N-substituted ethylenediamines in reductive amination periodate-oxidized Using this method, we obtained fluorescently labelled or biotinylated RNAs varying length (from 3 2000 nt) carrying different 5' ends (including...
Epilepsy is a common disorder of the brain characterized by spontaneous recurrent seizures, which develop gradually during process called epileptogenesis. The mechanistic processes underlying changes tissue and networks toward increased seizure susceptibility are not fully understood. In rodents, injection kainic acid (KA) ultimately leads to development epileptic reflecting similar neuropathological characteristics as seen in patients with temporal lobe epilepsy (TLE). Although this model...
Purpose: Resolution of inflammation is an active homeostatic process controlled by proresolving lipids and peptides.We characterized this during epileptogenesis to test whether boosting resolution mechanisms prevents or mediates disease modifications.Method: Our analyses were done in the hippocampus mice exposed status epilepticus (SE) their sham controls, patients who died ≤5 ≥7 days from SE autopsy controls.Mice studied 2 h, 24 h 72 after (epileptogenesis) evoked intraamygdala injection...
Abstract Fibroblast growth‐factor homologous factor ( FHF1 ) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients pathogenic variants. retrospectively collected clinical, genetic, neurophysiologic, neuroimaging data 17 ‐DEE. Sixteen had recurrent heterozygous missense variants: 14 p.Arg114His variant two...
Preclinical models of seizures and epilepsy in rodents contributed substantially to the discovery currently available antiseizure medications. These were also broadly used for investigation processes epileptogenesis. Nevertheless, rodent pose some limitations, thus, new using alternative species are high demand. The aim this study was describe a model seizures/epilepsy induced by cholinomimetic agent, pilocarpine (PILO), larval zebrafish.
Synaptic vesicle glycoprotein 2A (SV2A) regulates action potential-dependent neurotransmitter release and is commonly known as the primary binding site of an approved anti-epileptic drug, levetiracetam. Although several rodent knockout models have demonstrated importance SV2A for functional neurotransmission, its precise physiological function role in epilepsy pathophysiology remains to be elucidated. Here, we present a novel sv2a model zebrafish, vertebrate with complementary advantages...
Abstract In recent years there has been extensive research on malformations of cortical development (MCDs) that result in clinical features like developmental delay, intellectual disability, and drug-resistant epilepsy (DRE). Various studies highlighted the contribution microtubule-associated genes (including tubulin kinesin encoding genes) MCD development. It reported de novo mutations KIF2A , a member kinesin-13 family, are linked to brain DRE. Although it is known functions by regulating...
New pharmacological approaches that target orexin receptors (OXRs) are being developed to treat sleep disorders such as insomnia and narcolepsy, with fewer side effects than existing treatments. Orexins neuropeptides exert excitatory on postsynaptic neurons via the OXRs, important in regulating sleep/wake states. To date, there three FDA-approved dual receptor antagonists for treatment of insomnia, several small molecule oral OX2R (OXR type 2) agonists pipeline addressing deficiency...
Abstract Protein aggregation is an underappreciated mechanism that may contribute to the loss- and oncogenic-gain-of-function of mutant tumor suppressors such as p53 axin. In present study, we describe amyloid-like behaviour second most frequently mutated suppressor in human cancer, PTEN. silico analysis revealed a particularly high vulnerability for this protein, which was corroborated by vitro assays. cultured cells, found under stress conditions, PTEN readily undergoes result mutation....
Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by pathogenic variants in TSC1 and TSC2 genes. TSC patients present with seizures brain abnormalities such as tubers subependymal giant cells astrocytoma (SEGA). Despite common molecular clinical features, the severity of disease varies greatly, even intrafamilially. The second hit hypothesis suggests that an additional, inactivating mutation remaining functional allele causes more severe phenotype therefore explains...