A5039428258- Heat shock proteins research
- Computational Drug Discovery Methods
- Molecular Biology Techniques and Applications
- Genetic Neurodegenerative Diseases
- Biochemical effects in animals
- Traumatic Brain Injury and Neurovascular Disturbances
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- thermodynamics and calorimetric analyses
- Anesthesia and Neurotoxicity Research
- Machine Learning in Bioinformatics
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Cancer Research and Treatments
- Enzyme Structure and Function
- Spaceflight effects on biology
- Advanced Glycation End Products research
- Neuroscience of respiration and sleep
- Viral Infections and Immunology Research
- Cholinesterase and Neurodegenerative Diseases
- Nicotinic Acetylcholine Receptors Study
Institute of Cytology
2015-2024
Engelhardt Institute of Molecular Biology
2021
Aristotle University of Thessaloniki
2021
Russian Academy of Sciences
2011-2020
Howard Hughes Medical Institute
2020
New York University
2020
Klinik für Frauenheilkunde
2020
München Klinik
2020
Klinikum rechts der Isar
2020
St Petersburg University
2020
The key feature of polyglutamine aggregates accumulating in the course Huntington disease (HD) is their resistance to protein denaturants, and date only chaperones are proved prevent mutant aggregation. It was suggested that expanded chains (polyQ) huntingtin cross-linked other proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Here we clarify roles GAPDH molecular chaperone Hsp70 formation sodium dodecyl sulfate (SDS)-insoluble polyQ aggregates. First, addition pure found...
Macrophages constitute a major part of tumor microenvironment, and most existing data demonstrate their ruling role in the development anti-drug resistance cancer cell. One powerful protection system is based on heat shock proteins whose synthesis triggered by activated Heat Shock Factor-1 (HSF1); inhibition HSF1 with CL-43 sensitized A549 lung cells to anti-cancer effect etoposide. Notably, analyzing xenografts mice we observed nest-like pattern co-localization demonstrating enhanced...
Neuronal cell death at late stages of Alzheimer’s disease (AD) causes the release cytosolic proteins. One most abundant such proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forms stable aggregates with extracellular amyloid-β (Aβ). We detect these in cerebrospinal fluid (CSF) from AD patients levels directly proportional to progressive AD. found that GAPDH a covalent bond Q15 Aβ is mediated by transglutaminase (tTG). The Q15A substitution weakens interaction between and reduces...
Abstract Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly renewing cancer cells, making it an important target for therapeutic compounds. To date several inhibitors are presented with remarkable anticancer activity, however their clinical application is limited by the high toxicity towards normal cells. This study aimed to develop assays search substances that reduce activity of diminish its protective function On our mind resulting compounds alone should be safe...
The Hsp70 chaperone binds and inhibits proteins implicated in apoptotic signaling including Caspase-3. Induction of apoptosis is an important mechanism anti-cancer drugs, therefore can act as a protective system tumor cells against therapeutic agents. In this study we present assessment candidate compounds that are able to dissociate the complex with Caspase-3, thus sensitize drug-induced apoptosis. Using PASS program for prediction biological activity selected derivative benzodioxol (BT44)...
Proteins with long polyglutamine repeats form a complex glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), which enhances aggregation and cytotoxicity in models of Huntington disease. The aim this study was to develop novel assay for the screening anti‐aggregation compounds focus on aggregation‐promoting capacity GAPDH. includes pure Q58 fragment, GAPDH, transglutaminase that links two proteins. feasibility new verified using GAPDH binders, hydroxynonenal −(−)deprenyl, benzothiazole...
The chaperone system based on Hsp70 and proteins of the DnaJ family is known to protect tumor cells from a variety cytotoxic factors, including anti-tumor therapy. To analyze whether this also functions in highly malignant brain tumor, we knocked down expression (HSPA1A) its two most abundant co-chaperones, Hdj1 (DNAJB1) Hdj2 (DNAJA1) C6 rat glioblastoma cell line. As expected, depletion caused substantial reduction growth rate increased survival tumor-bearing animals, whereas had no effect....
Most neurodegenerative pathologies stem from the formation of aggregates mutant proteins, causing dysfunction and ultimately neuronal death. This study was aimed at elucidating role protein factors that promote aggregate or prevent process, respectively, glyceraldehyde-3-dehydrogenase (GAPDH) tissue transglutaminase (tTG) Hsp70 molecular chaperone. The siRNA technology used to show inhibition GAPDH expression leads a 4550% reduction in aggregation huntingtin, with repeat 103 glutamine...
Hypoxia, which commonly accompanies tumor growth, depending on its strength may cause the enhancement of tumorigenicity cancer cells or their death. One proteins targeted by hypoxia is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and we demonstrated here that mimicked treating C6 rat glioblastoma with cobalt chloride caused an up-regulation enzyme expression, while further elevation hypoxic stress aggregation concomitantly cell Reduction GAPDH performed aid specific shRNAs resulted in...
The common feature of Huntington disease is the accumulation oligomers or aggregates mutant huntingtin protein (mHTT), which causes death a subset striatal neuronal populations. cytotoxic species can leave neurons and migrate to other groups cells penetrating damaging them in prion-like manner. We hypothesized that glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), previously shown elevate aggregation mHTT, associated with an increased efficiency intercellular propagation...
The risk of progression most sporadic neurodegenerative diseases, including Alzheimer's disease, increases with age. Traditionally, this is associated a decrease in the efficiency cell protection systems, particular, molecular chaperones. Thus, development small molecules able to induce synthesis chaperones promising therapeutic approach prevent neural diseases ageing. Here, we describe new compound IA-50, belonging class indolylazines and featured by low size topological polar surface area,...
The new derivatives of mono- and bis-1,2,4-triazoloazines were obtained. cytotoxic activity the compounds was evaluated against cancer cell lines.
Abstract Background Cancer recurrence is regulated by a variety of factors, among which the material dying tumor cells; it suggested that remaining after anti-cancer therapy cells receive signal from proteins called damage-associated molecular patterns (DAMPs), one heat shock protein 70 (Hsp70). Methods Two models repopulation were employed, based on minimal population cancer and application conditioned medium (CM). To deplete CMs Hsp70 affinity chromatography ATP-agarose immunoprecipitation...