A5019648144- Ion Channels and Receptors
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Zebrafish Biomedical Research Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Neurobiology and Insect Physiology Research
- Epilepsy research and treatment
- Neuroendocrine Tumor Research Advances
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Pharmacological Receptor Mechanisms and Effects
- Circadian rhythm and melatonin
- Nuclear Receptors and Signaling
- Antioxidant Activity and Oxidative Stress
- Retinoids in leukemia and cellular processes
- Nicotinic Acetylcholine Receptors Study
- Biochemical Analysis and Sensing Techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- Adenosine and Purinergic Signaling
- Neonatal and fetal brain pathology
- Dendrimers and Hyperbranched Polymers
- Pharmacogenetics and Drug Metabolism
- Postharvest Quality and Shelf Life Management
University of Pecs
2019-2024
Semmelweis University
2022
KU Leuven
2013-2019
National Institutes of Health
2011
National Institute of Diabetes and Digestive and Kidney Diseases
2011
Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms childhood epilepsy syndromes. Distinct de novo mutations in SCN1A gene are responsible for over 80% DS cases. While largely resistant to treatment with existing anti-epileptic drugs, promising results have been obtained clinical trials human patients treated serotonin agonist fenfluramine as an add-on therapeutic. We developed a zebrafish model using morpholino antisense oligomers (MOs) targeting scn1Lab,...
Dravet syndrome (DS) is a severe epilepsy that starts within the first year of life. In clinical study, add-on treatment with fenfluramine, potent 5-hydroxytryptamine (5-HT) releaser activating multiple 5-HT receptor subtypes, made 70% DS children seizure free. Others and we recently confirmed efficacy fenfluramine as an antiepileptiform compound in zebrafish models DS. By using large set subtype selective agonists, this study examined which subtypes can be targeted to trigger antiseizure...
Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) vanilloid (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression increased some malignancies. In our study we aim to characterize the functionality TRPA1 TRPV1 human mouse osteosarcoma tissues cell line. TRPA1/Trpa1 TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel...
Nanomaterials are being extensively produced and applied in society. Human environmental exposures are, therefore, inevitable so increased attention is given to nanotoxicity. While silica nanoparticles (NP) one of the top five nanomaterials found consumer biomedical products, their toxicity profile poorly characterized. In this study, we investigated with diameters 20, 50 80 nm using an vivo zebrafish platform that analyzes multiple endpoints related developmental, cardio-, hepato-,...
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...
Oral squamous cell carcinoma (OSCC) is a common cancer with poor prognosis. Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid (TRPV1) receptors are non-selective cation channels expressed on primary sensory neurons epithelial immune cells. TRPV1 mRNA immunopositivity, as well TRPA1-like immunoreactivity upregulation, were demonstrated in OSCC, but selectivity problems the antibodies still raise questions their functional relevance unclear. Therefore, here, we investigated TRPA1...
The neuropathological background of major depression and anxiety as non-motor symptoms Parkinson's disease is much less understood than classical motor symptoms. Although, neurodegeneration the Edinger-Westphal nucleus in human a known phenomenon, its possible significance mood status has never been elucidated. In this work we aimed at investigating whether neuron loss alpha-synuclein accumulation urocortin 1 containing (UCN1) cells centrally-projecting (EWcp) associated with depression-like...
<h3>Background:</h3> Transient receptor potential ankyrin 1 (TRPA1), a cation channel, is expressed predominantly in primary sensory neurons, but its central distribution and role mood control are not well understood. We investigated whether TRPA1 the urocortin (UCN1)–immunoreactive centrally projecting Edinger–Westphal nucleus (EWcp), we hypothesized that chronic variable mild stress (CVMS) would reduce expression mice. anticipated <i>TRPA1</i> mRNA be present human EWcp, it downregulated...
Somatostatin is an important mood and pain-regulating neuropeptide, which exerts analgesic, anti-inflammatory, antidepressant effects via its Gi protein-coupled receptor subtype 4 (SST4) without endocrine actions. SST4 suggested to be a unique novel drug target for chronic neuropathic pain, depression, as common comorbidity. However, neuronal expression cellular mechanism are poorly understood. Therefore, our goals were (i) elucidate the pattern of Sstr4/SSTR4 mRNA, (ii) characterize...
The striatum is an essential component of the basal ganglia that involved in motor control, action selection and learning. pathophysiological changes are present several neurological psychiatric disorder including Parkinson's Huntington's diseases. striatal cholinergic neurons main regulators microcircuitry. It has been demonstrated estrogen exerts various effects on neuronal functions dopaminergic medium spiny (MSN), however little known about how activity interneurons influenced by...
A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from central terminals afferents sensitize secondary nociceptive nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization chronic orofacial pain migraine. In present study, we investigated newest member tachykinin family, hemokinin-1 (HK-1) encoded by Tac4...
The Transient Receptor Potential Vanilloid 1 (TRPV1) non-selective cation channel predominantly expressed in primary sensory neurons of the dorsal root and trigeminal ganglia mediates pain neurogenic inflammation. TRPV1 mRNA immunoreactivity were described central nervous system (CNS), but its precise expression pattern function have not been clarified. Here we investigated Trpv1 mouse brain using ultrasensitive RNAScope situ hybridization. role anxiety, depression-like behaviors memory...
Previously, G protein-coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high affinity and selectivity. Here, we prepared GPCR ligand–dendrimer (GLiDe) conjugates a potent adenosine (AR) antagonist; such agents are of interest for treating Parkinson's disease, asthma, other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on extended C8 substituent coupling by Cu(I)-catalyzed click chemistry azide-derivatized G4...
Transient Receptor Potential Vanilloid 1 and Ankyrin (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons regulate nociceptor inflammatory functions. Resolvins endogenous lipid mediators. Resolvin D1 (RvD1) is described as a selective inhibitor of TRPA1-related postoperative pain mice acting on the G protein-coupled receptor DRV1/GPR32. D2 (RvD2) very potent TRPV1 TRPA1 DRG neurons, decreases GPR18 receptor, via TRPV1/TRPA1-independent mechanisms. We provided...
Somatostatin receptor subtype 4 (SST4) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed be a novel target for drug development. To overcome the species differences of SST4 expression function between humans mice, we generated an humanized mouse line serve as translational animal model preclinical research. A transposon vector containing hSSTR4 reporter gene construct driven by regulatory elements were...
Pharmacotherapy of neuropathic pain is still challenging. Our earlier work indicated an analgesic effect dimethyl trisulfide (DMTS), which was mediated by somatostatin released from nociceptor nerve endings acting on SST4 receptors. Somatostatin release occurred due to TRPA1 ion channel activation. In the present study, we investigated DMTS in evoked partial ligation sciatic mice. Expression mRNA Trpa1 murine dorsal-root-ganglion neurons detected RNAscope. Involvement channels and receptors...
Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one major hallmarks temporal lobe epilepsy (TLE). The vulnerability mossy TLE well known animal models as patients; however, mechanisms leading to cellular death unclear.Transient receptor potential melastatin 4 (TRPM4) Ca2+-activated non-selective cation channel regulating diverse physiological functions excitable cells. Here, we identified that TRPM4 present hilar regulates...
Transient receptor potential ankyrin 1 (TRPA1), a nonselective cation channel, contributes to several (patho)physiological processes. Smell loss is an early sign in neurodegenerative disorders, such as multiple sclerosis, Parkinson's and Alzheimer's diseases; therefore, we focused on its role olfaction social behaviour with the aim reveal therapeutic use. The presence of Trpa1 mRNA was studied along olfactory tract mice by combined RNAscope situ hybridisation immunohistochemistry. aversive...
Drug-induced liver injury (DILI) is the most common reason for failures during drug development process and safety-related withdrawal of drugs from pharmaceutical market. Therefore, having tools techniques that can detect hepatotoxic properties in candidates at an early discovery stage highly desirable. In this study, cell imaging counting was used to measure a fast, straightforward, unbiased way effect paracetamol tetracycline, (compounds known cause hepatotoxicity humans) on amount...
Background: Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via its receptor subtype 4 (SST ) without influencing endocrine functions. Therefore, SST is considered to be a novel target for drug development in pain, especially chronic neuropathy which great unmet medical need. Purpose Experimental Approach: Here, we examined silico binding, -linked G protein activation β-arrestin on stable expressing cells of our...
The Tac4 gene-derived hemokinin-1 (HK-1) binds to the NK1 receptor, similarly Substance P, and plays a role in acute stress reactions pain transmission mice. Here we investigated mRNA expression pain-related regions its involvement chronic restraint stress-evoked behavioral changes using gene-deleted (Tac4-/-) mice compared C57Bl/6 wildtypes (WT). was detected by situ hybridization RNAscope technique. Touch sensitivity assessed esthesiometry, cold tolerance paw withdrawal latency from 0°C...
All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders malignancies. ATRA prone to isomerization oxidation, which can affect its activity selectivity. Novel diphenylacetylene-based analogues with increased stability help overcome these problems may offer significant potential as therapeutics variety cancers neurodegenerative diseases,...