A5090070043- Ubiquitin and proteasome pathways
- Parkinson's Disease Mechanisms and Treatments
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Genetic Neurodegenerative Diseases
- Genomics and Chromatin Dynamics
- Alzheimer's disease research and treatments
- Calcium signaling and nucleotide metabolism
- Cutaneous Melanoma Detection and Management
- Neonatal Health and Biochemistry
- Neurogenesis and neuroplasticity mechanisms
- Pancreatic function and diabetes
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- RNA regulation and disease
- Melanoma and MAPK Pathways
- Microbial Inactivation Methods
- Cancer and Skin Lesions
University of Szeged
2006-2025
Institute of Sociology
2024
University of Debrecen
2023-2024
University of Johannesburg
2023-2024
HUN-REN Research Centre for Natural Sciences
2013-2024
J. Selye University
2024
Tomas Bata University in Zlín
2024
John von Neumann University
2024
Vysoká škola manažmentu, City University of Seattle
2024
Institute of Molecular Life Sciences
2013-2023
Abstract Sirtuins are a highly conserved class of NAD + -dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis cancer, inflammation and neurodegeneration, which makes modulation activity promising strategy for pharmaceutical intervention. A rational basis development optimized inhibitors is lacking so far. Here we present high-resolution structures complex with selective drug-like that show unique inhibitory mechanism. Potency unprecedented selectivity...
Here we report the development of a proteolysis targeting chimera (PROTAC) based on combination unique features sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, bona fide cereblon ligand. For first time, formation PROTAC by Cu(I)-catalyzed cycloaddition thalidomide-derived azide to an alkynylated inhibitor. This well versatile linking strategy can be readily adapted other targets. In HeLa cells, our SirReal-based induced...
The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein Parkinson disease multiple system atrophy, respectively; however, co-occurrence of β-amyloid (Aβ) human brain has been recently reported, suggesting the existence mixed type pathologies that could result obstacles correct diagnosis treatment. Here we identified TPPP/p25 as an interacting partner soluble Aβ oligomers major risk factors for Alzheimer...
Previously, we have demonstrated the presence of a protein factor [tubulin polymerization perturbing (TPPP)] in brain and neuroblastoma cell but not muscle extract that uniquely influences microtubule assembly. Here describe procedure for isolation this from cytosolic fraction bovine present evidence is target both tubulin microtubules vitro. The crucial step purification cationic exchange chromatography; bound TPPP eluted at high salt concentrations, indicating basic character protein. By...
TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and aligned along the network transfected mammalian cells. In normal human brain, expressed predominantly oligodendrocytes, where its expression proved to be crucial for their differentiation process. Here we demonstrated of HeLa cells, doxycycline-inducible CHO10 oligodendrocyte CG-4 cells promoted acetylation alpha-tubulin at residue Lys-40, whereas...
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and substrate proteins. Dysregulation human Sirt2 (hSirt2) activity has been associated with pathogenesis cancer, inflammation, neurodegeneration, which makes modulation hSirt2 a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently discovered by us as highly potent isotype-selective inhibitors....
Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this differs other proteins so far; however, it shows high homology with p25-like hypothetical sought via blast . Here, characterized the binding to by means surface plasmon resonance; kinetic parameters are follows: k on , 2.4 × 10 4 M –1 ·s ; off 5.4 –3 s K d 2.3 –7 M. This at substoichometric concentration promotes...
TPPP/p25 is a brain-specific protein, which induces tubulin polymerization and microtubule (MT) bundling enriched in Lewy bodies characteristic of Parkinson's disease [Tirián et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13976−13981]. We identified two human gene sequences, CG1−38 p25β, encoded homologous proteins, that we termed p20 p18, respectively. These proteins display 60% identity with promoting protein/p25 (TPPP/p25); however, the N-terminal segment missing. They could be...
Abstract Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) located in OG aggregates oligodendroglial cytoplasmic inclusions multiple atrophy. We developed a novel monoclonal anti‐TPPP/p25 antibody to quantify different subtypes...
Twenty adult individuals with chronic leg ulcers caused by venous insufficiency, and 5 patients full-thickness burns were treated. of the (15 burns) grafted separated autologous keratinocytes. In these cases cells fixed to wound bed a fibrin net. Five other (with ulcers) treated without 16 20 keratinocytes in net, defect healed completely 14 21 days. On hand, net failed significantly accelerate process reepithelialization. Our experience suggests that rapid healing skin defects can be...
Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, formation of inclusions caused mutation huntingtin protein and its relationship with changes in energy metabolism pathological were investigated both transgenic 3-nitropropionic acid-treated mouse models for HD. The HD normal mice clinically; affected brain regions identified immunohistochemistry used...
TPPP/p25, the first representative of a new protein family, identified as brain-specific unfolded induces aberrant microtubule assemblies in vitro, suppresses mitosis Drosophila embryo and is accumulated inclusion bodies human pathological brain tissues. In this paper, we present prediction additional experimental data that validate TPPP/p25 to be member "intrinsically unstructured" family. The comparison these characteristics with alpha-synuclein tau, involved also neurodegenerative...
<title>Abstract</title> Background The rising prevalence of cutaneous and subcutaneous tumors has driven interest in electrochemotherapy (ECT) as a potential treatment. However, patient-reported outcomes remain underexplored. Objectives This study aims to assess the impact ECT on quality life (QoL) patients, addressing gap current literature. Methods A prospective evaluated 62 patients treated with between 2015 2022. QoL was measured using EQ-5D-3L questionnaire, calculating EQ-5D-index...
Abstract The rising prevalence of cutaneous and subcutaneous tumors has driven interest in electrochemotherapy (ECT) as a potential treatment. However, patient-reported outcomes remain underexplored. This study aims to assess the short-term impact ECT on quality life (QoL) patients, addressing gap current literature. A prospective evaluated 62 patients treated with between 2015 2022. QoL was measured using EQ-5D-3L questionnaire, calculating EQ-5D-index assessing health state (EQ-VAS) pain...
Internationalizing a company is particularly challenging for micro-enterprises and SMEs due to the limited resources available managing strategic activities. This paper aimed create model of factors influencing internationalization process from Central Europe. The study employed principal component analysis identify latent components model, namely innovation, management (SM), barriers. their relationships were analyzed using Logit regression ANOVA. Additionally, influence two control...
Triosephosphate isomerase (TPI) deficiency is a unique glycolytic enzymopathy coupled with neurodegeneration. Two Hungarian compound heterozygote brothers inherited the same TPI mutations (F240L and E145Stop), but only younger one suffers from In present study, we determined kinetic parameters of key enzymes including mutant for rational modelling erythrocyte glycolysis. We found that low activity in cells (lower than predicted protein level specific purified recombinant enzyme) an increase...
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of microtubule system plays a crucial role in differentiation oligodendrocytes. Here we first demonstrated by multinuclear NMR that extended segments are localized at N- C-terminals straddling flexible region. We showed affinity chromatography, fluorescence spectroscopy circular dichroism GTP binds to TPPP/p25 likely within region; neither positions nor intensities peaks assigned...