TY - JOUR AU - Bakonyi, Péter AU - Kolonics, Attila AU - Aczél, Dóra Tímea AU - Zhou, Lei AU - Mozaffaritabar, Soroosh AU - Molnár, Kinga AU - László, Lajos AU - Kutasi, Balazs AU - Tanisawa, Kumpei AU - Park, Jonguk AU - Gu, Yaodong AU - Pinho, Ricardo A. AU - Radák, Zsolt TI - Voluntary exercise does not increase gastrointestinal motility but increases spatial memory, intestinal eNOS, Akt levels, and Bifidobacteria abundance in the microbiome JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 14 PY - 2023 SN - 1664-042X DO - 10.3389/fphys.2023.1173636 UR - https://m2.mtmt.hu/api/publication/34126507 ID - 34126507 N1 - Összes idézések száma a WoS-ban: 0 AB - The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain–exercise–intestine–microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VO 2 max on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS). Eight weeks of voluntary running increased VO 2 max, and spatial memory was assessed by the Morris maze test but did not significantly change the motility of the gastrointestinal tract or production of ROS in the intestine. The protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) protein levels significantly increased in the intestine, while peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NFR1), SIRT1, SIRT3, nicotinamide phosphoribosyl transferase (NAMPT), and nuclear factor κB (NF-κB) did not change. On the other hand, voluntary exercise increased the number of caveolae in the smooth muscles of the intestine and relative abundance of Bifidobacteria in the microbiome, which correlated with the Akt levels in the intestine. Voluntary exercise has systemic effects and the relationship between intestinal Akt and the microbiome of the gastrointestinal tract could be an important adaptive response. LA - English DB - MTMT ER - TY - JOUR AU - Kasi, Phanindra Babu AU - Molnár, Kinga AU - László, Lajos AU - Kotormán, Márta TI - Peppermint extract inhibits protein aggregation JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 72 PY - 2021 IS - 3 SP - 367 EP - 372 PG - 6 SN - 2676-8615 DO - 10.1007/s42977-021-00086-0 UR - https://m2.mtmt.hu/api/publication/31998803 ID - 31998803 LA - English DB - MTMT ER - TY - JOUR AU - Kobolák, Julianna AU - Teglasi, Annamaria AU - Bellák, Tamás AU - Janstova, Zofia AU - Molnár, Kinga AU - Zana, Melinda AU - Bock, Istvan AU - László, Lajos AU - Dinnyés, András TI - Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres are Suitable for Neurotoxicity Screening JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 5 PG - 28 SN - 2073-4409 DO - 10.3390/cells9051122 UR - https://m2.mtmt.hu/api/publication/31307709 ID - 31307709 N1 - Funding Agency and Grant Number: European Union's Horizon 2020 research and innovation programme [681002] Funding text: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 681002 (EU-ToxRisk). AB - We present a hiPSC-based 3D in vitro system suitable to test neurotoxicity (NT). Human iPSCs-derived 3D neurospheres grown in 96-well plate format were characterized timewise for 6-weeks. Changes in complexity and homogeneity were followed by immunocytochemistry and transmission electron microscopy. Transcriptional activity of major developmental, structural, and cell-type-specific markers was investigated at weekly intervals to present the differentiation of neurons, astrocytes, and oligodendrocytes. Neurospheres were exposed to different well-known toxicants with or without neurotoxic effect (e.g., paraquat, acrylamide, or ibuprofen) and examined at various stages of the differentiation with an ATP-based cell viability assay optimized for 3D-tissues. Concentration responses were investigated after acute (72 h) exposure. Moreover, the compound-specific effect of rotenone was investigated by a panel of ER-stress assay, TUNEL assay, immunocytochemistry, electron microscopy, and in 3D-spheroid based neurite outgrowth assay. The acute exposure to different classes of toxicants revealed distinct susceptibility profiles in a differentiation stage-dependent manner, indicating that hiPSC-based 3D in vitro neurosphere models could be used effectively to evaluate NT, and can be developed further to detect developmental neurotoxicity (DNT) and thus replace or complement the use of animal models in various basic research and pharmaceutical applications. LA - English DB - MTMT ER - TY - JOUR AU - Kobolák, Julianna AU - Molnár, Kinga AU - Varga, E AU - Bock, István AU - Jezsó, Bálint AU - Téglási, A AU - Zhou, S AU - Lo Giudice, M AU - Hoogeveen-Westerveld, M AU - Pijnappel, WWM P AU - Phanthong, P AU - Varga, N AU - Kitiyanant, N AU - Freude, K AU - Nakanishi, H AU - László, Lajos AU - Hyttel, P AU - Dinnyés, András TI - Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells JF - EXPERIMENTAL CELL RESEARCH J2 - EXP CELL RES VL - 380 PY - 2019 IS - 2 SP - 216 EP - 233 PG - 18 SN - 0014-4827 DO - 10.1016/j.yexcr.2019.04.021 UR - https://m2.mtmt.hu/api/publication/30656315 ID - 30656315 N1 - Funding Agency and Grant Number: European Union [PIAPP-GA-2011-286264, PIAPP-GA-2012-324451, PITN-GA-2012-317146]; Marie Sklodowska-Curie Actions of the European Union's Horizon 2020 programme under REA grant [675228] Funding text: This work was supported by grants from European Union's FP7PEOPLE programme (Anistem, PIAPP-GA-2011-286264; STEMMAD, PIAPP-GA-2012-324451; EpiHealthNet, PITN-GA-2012-317146). Maria Lo Giudice has received funding from 'The CaSR Biomedicine Network' from the Marie Sklodowska-Curie Actions of the European Union's Horizon 2020 programme under REA grant agreement no. 675228. BioTalentum Ltd., Gödöllő, 2100, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, 1117, Hungary Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 1870, Denmark Department of Clinical Genetics, Erasmus MC Rotterdam, Rotterdam, 3015 CN, Netherlands Institute of Molecular Biosciences, Mahidol University, Bangkok, 73170, Thailand Department of Metabolic Diseases, Heim Pál Children's Hospital, Budapest, 1089, Hungary Department of Macromolecular Science and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Kyoto, 606-8585, Japan Molecular Animal Biotechnology Laboratory, Szent István University, Gödöllő, 2101, Hungary Export Date: 29 August 2019 CODEN: ECREA Correspondence Address: Dinnyés, A.; BioTalentum Ltd., Aulich L. u. 26, Hungary; email: Manuscript.Dinnyes@biotalentum.hu BioTalentum Ltd., Gödöllő, 2100, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, 1117, Hungary Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 1870, Denmark Department of Clinical Genetics, Erasmus MC Rotterdam, Rotterdam, 3015 CN, Netherlands Institute of Molecular Biosciences, Mahidol University, Bangkok, 73170, Thailand Department of Metabolic Diseases, Heim Pál Children's Hospital, Budapest, 1089, Hungary Department of Macromolecular Science and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Kyoto, 606-8585, Japan Molecular Animal Biotechnology Laboratory, Szent István University, Gödöllő, 2101, Hungary Export Date: 25 November 2019 CODEN: ECREA Correspondence Address: Dinnyés, A.; BioTalentum Ltd., Aulich L. u. 26, Hungary; email: Manuscript.Dinnyes@biotalentum.hu LA - English DB - MTMT ER - TY - JOUR AU - Kasi, Phanindra Babu AU - Borics, Attila AU - Varga, Mónika AU - Endre, Gábor AU - Molnár, Kinga AU - László, Lajos AU - Kotormán, Márta TI - Grapefruit Seed Extract Inhibits the Formation of Amyloid-like Fibrils by Trypsin in Aqueous Ethanol JF - NATURAL PRODUCT COMMUNICATIONS J2 - NAT PROD COMMUN VL - 13 PY - 2018 IS - 11 SP - 1437 EP - 1440 PG - 4 SN - 1934-578X DO - 10.1177/1934578X1801301106 UR - https://m2.mtmt.hu/api/publication/30418445 ID - 30418445 AB - Several natural compounds deriving from plants are known to be efficient anti-amyloid aggregation agents. In this study, anti-aggregation activity of grapefruit seed extract was investigated using trypsin as a model protein in aqueous ethanol at pH 7.0. Using turbidity measurement, Congo red (CR) binding assay, electronic circular dichroism (ECD) and transmission electron microscopy (TEM), we found that grapefruit seed extract has ability to inhibit trypsin amyloidlike fibril formation in vitro, and effectiveness increases with growing concentration of grapefruit seed extract. The total phenolic content of it was determined. The results showed that in addition to the polyphenolic compounds some other compounds are also responsible for the fibril formation inhibitory effect. We indicated it for the first time that limonin has anti-fibrillation effect. LA - English DB - MTMT ER - TY - JOUR AU - Kasi, Phanindra Babu AU - Borics, Attila AU - Molnár, Kinga AU - László, Lajos AU - Kotormán, Márta TI - Eduscho coffee extract effectively inhibits the formation of amyloid-like fibrils by trypsin in aqueous ethanol JF - NATURAL PRODUCT COMMUNICATIONS J2 - NAT PROD COMMUN VL - 13 PY - 2018 IS - 12 SP - 1695 EP - 1698 PG - 4 SN - 1934-578X DO - 10.1177/1934578x1801301229 UR - https://m2.mtmt.hu/api/publication/30403247 ID - 30403247 LA - English DB - MTMT ER - TY - JOUR AU - Kasi, Phanindra Babu AU - Kotormán, Márta AU - Borics, Attila AU - Hervay, BG AU - Molnár, Kinga AU - László, Lajos TI - The Inhibitory Effect of Panax Ginseng Extract on Amyloid-like Fibril Formation of Trypsin in Aqueous Ethanol JF - PROTEIN AND PEPTIDE LETTERS J2 - PROTEIN PEPTIDE LETT VL - 25 PY - 2018 IS - 3 SP - 253 EP - 259 PG - 7 SN - 0929-8665 DO - 10.2174/0929866525666171229231226 UR - https://m2.mtmt.hu/api/publication/3381215 ID - 3381215 N1 - : EMIRATES AB - Background: In case of several chronic diseases, prevention is could be more effective than treatment. Functional foods that contain significant amounts of bioactive components gained considerable attention not only in traditional but in modern medicine as well. We have investigated how P. ginseng extract inhibits the in vitro formation of amyloid-like fibrils of phenylmethylsulfonyl-trypsin (PMS-trypsin) in 60% ethanol at pH 7.0. The model system used is non-physiological, but it is capable of detecting the anti-amyloidogenic effect of the various agents. Objective: The main objective of this study was to examine the possible inhibitory effect of ginseng extract on amyloid-like fibril formation of trypsin in aqueous ethanol. Methods: The amyloid formation and aggregation kinetics of PMS-trypsin was studied by turbidity measurements, Congo Red (CR) binding assays, size exclusion chromatography and Electronic Circular Dichroism (ECD) measurements and the shapes of amyloid fibrils became visible by Transmission Electron Microscopy (TEM). Results: In the presence of 500-fold diluted P. ginseng extract in the incubation mixture, the absorption at 350 nm decreased to 47.1% after incubation for 24 h, compared relative to the sample which contained no additives. CR binding experiments suggested that the aggregates in our samples have amyloid-like properties, and P. ginseng extract inhibits the amyloid-like fibril formation of PMS-trypsin depending on concentration. Our results show that the ginseng extract does not bind to the fibrils. In the absence of P. ginseng extracts large sized colloid aggregates were abundant. Adding P. ginseng extracts to our samples decreased the light dispersion of the solution. This is due to the decrease of the rate of the aggregation or to the smaller size of the aggregates evolved. Our results show that the presence of ginseng extract helps to maintain the native structure of the protein. In the presence of 500-fold diluted P. ginseng extract, TEM images demonstrated, that P. ginseng extract has inhibitory effect on the formation of amyloid-like fibrils of PMS-trypsin. Conclusion: The results indicated that P. ginseng extract significantly inhibits the formation of amyloid-like fibrils of PMS-trypsin in aqueous ethanol, and helps to maintain the native structure of the protein. The rate of inhibition depends on concentration. P. ginseng extract is an efficient antiamyloidogenic agent. LA - English DB - MTMT ER - TY - JOUR AU - Sukseree, S AU - László, Lajos AU - Gruber, F AU - Bergmann, S AU - Narzt, MS AU - Nagelreiter, IM AU - Höftberger, R AU - Molnár, Kinga AU - Rauter, G AU - Birngruber, T AU - Larue, L AU - Kovács, Gábor Géza AU - Tschachler, E AU - Eckhart, L TI - Filamentous Aggregation of Sequestosome-1/p62 in Brain Neurons and Neuroepithelial Cells upon Tyr-Cre-Mediated Deletion of the Autophagy Gene Atg7 JF - MOLECULAR NEUROBIOLOGY J2 - MOL NEUROBIOL VL - 55 PY - 2018 IS - 11 SP - 8425 EP - 8437 PG - 13 SN - 0893-7648 DO - 10.1007/s12035-018-0996-x UR - https://m2.mtmt.hu/api/publication/3354850 ID - 3354850 AB - Defects in autophagy and the resulting deposition of protein aggregates have been implicated in aging and neurodegenerative diseases. While gene targeting in the mouse has facilitated the characterization of these processes in different types of neurons, potential roles of autophagy and accumulation of protein substrates in neuroepithelial cells have remained elusive. Here we report that Atg7f/fTyr-Cre mice, in which autophagy-related 7 (Atg7) is conditionally deleted under the control of the tyrosinase promoter, are a model for accumulations of the autophagy adapter and substrate sequestosome-1/p62 in both neuronal and neuroepithelial cells. In the brain of Atg7f/fTyr-Cre but not of fully autophagy competent control mice, p62 aggregates were present in sporadic neurons in the cortex and other brain regions as well in epithelial cells of the choroid plexus and the ependyma. Western blot analysis confirmed a dramatic increase of p62 abundance and formation of high-molecular weight species of p62 in the brain of Atg7f/fTyr-Cre mice relative to Atg7f/f controls. Immuno-electron microscopy showed that p62 formed filamentous aggregates in neurons and ependymal cells. p62 aggregates were also highly abundant in the ciliary body in the eye. Atg7f/fTyr-Cre mice reached an age of more than 2 years although neurological defects manifesting in abnormal hindlimb clasping reflexes were evident in old mice. These results show that p62 filaments form in response to impaired autophagy in vivo and suggest that Atg7f/fTyr-Cre mice are a model useful to study the long-term effects of autophagy deficiency on the homeostasis of different neuroectoderm-derived cells. © 2018 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Puska, Gina AU - Lutz, MI AU - Molnár, Kinga AU - Regelsberger, G AU - Ricken, G AU - Pirker, W AU - László, Lajos AU - Kovács, Gábor Géza TI - Lysosomal response in relation to α-synuclein pathology differs between Parkinson's disease and multiple system atrophy JF - NEUROBIOLOGY OF DISEASE J2 - NEUROBIOL DIS VL - 114 PY - 2018 SP - 140 EP - 152 PG - 13 SN - 0969-9961 DO - 10.1016/j.nbd.2018.02.019 UR - https://m2.mtmt.hu/api/publication/3349392 ID - 3349392 N1 - Funding Agency and Grant Number: Austrian-Hungarian Action Foundation [90ou11] Funding text: This study was partly supported by the Austrian-Hungarian Action Foundation (No 90ou11; to G.G.K., L.L., M.I.L., K.M., G. P.). Confocal microscopic work was performed in the Core Facility Imaging, Medical University Vienna. AB - Intracellular deposition of pathologically altered α-synuclein mostly in neurons characterises Parkinson's disease (PD), while its accumulation predominantly in oligodendrocytes is a feature of multiple system atrophy (MSA). Recently a prion-like spreading of pathologic α-synuclein has been suggested to play a role in the pathogenesis of PD and MSA. This implicates a role of protein processing systems, including lysosomes, supported also by genetic studies in PD. However, particularly for MSA, the mechanism of cell-to-cell propagation of α-synuclein is yet not fully understood. To evaluate the significance of lysosomal response, we systematically compared differently affected neuronal populations in PD, MSA, and non-diseased brains using morphometric immunohistochemistry (cathepsin D), double immunolabelling (cathepsin D/α-synuclein) laser confocal microscopy, and immunogold electron microscopy for the disease associated α-synuclein. We found that i) irrespective of the presence of neuronal inclusions, the volume density of cathepsin D immunoreactivity significantly increases in affected neurons of the pontine base in MSA brains; ii) volume density of cathepsin D immunoreactivity increases in nigral neurons in PD without inclusions and with non-ubiquitinated pre-aggregates of α-synuclein, but not in neurons with Lewy bodies; iii) cathepsin D immunoreactivity frequently colocalises with α-synuclein pre-aggregates in nigral neurons in PD; iv) ultrastructural observations confirm disease-associated α-synuclein in neuronal and astrocytic lysosomes in PD; v) lysosome-associated α-synuclein is observed in astroglia and rarely in oligodendroglia and in neurons in MSA. Our observations support a crucial role for the neuronal endosomal-lysosomal system in the processing of α-synuclein in PD. We suggest a distinct contribution of lysosomes to the pathogenesis of MSA, including the possibility of oligodendroglial and eventually neuronal uptake of exogenous α-synuclein in MSA. © 2018 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Chandrasekaran, A AU - Avci, HX AU - Ochalek, A AU - Rosingh, LN AU - Molnár, Kinga AU - László, Lajos AU - Bellák, Tamás AU - Teglasi, A AU - Pesti, Krisztina AU - Mike, Árpád AU - Phanthong, P AU - Biró, Orsolya AU - Hall, V AU - Kitiyanant, N AU - Krause, KH AU - Kobolák, Julianna AU - Dinnyés, András TI - Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells JF - STEM CELL RESEARCH J2 - STEM CELL RES VL - 25 PY - 2017 SP - 139 EP - 151 PG - 13 SN - 1873-5061 DO - 10.1016/j.scr.2017.10.010 UR - https://m2.mtmt.hu/api/publication/3312483 ID - 3312483 N1 - BioTalentum Ltd, Gödöllő, Hungary Department of Anatomy, Embryology and Histology, Faculty of Medicine, University of Szeged, Szeged, Hungary Molecular Animal Biotechnology Lab, Szent István University, Gödöllő, Hungary Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary Opto-Neuropharmacology Group, MTA-ELTE NAP B, Budapest, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary Stem Cell Research Group, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom Bangkok, Thailand First Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary Department of Veterinary and Animal Science, University of Copenhagen, Denmark Cited By :88 Export Date: 9 April 2024 Correspondence Address: Dinnyés, A.; BioTalentum LtdHungary; email: Manuscript.Dinnyes@biotalentum.hu AB - Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells and the derived neurons exhibited longer neurites. In contrast, 2D neural induction resulted in more SOX1 positive cells. While 2D monolayer induction resulted in slightly less mature neurons, at an early stage of differentiation, the patch clamp analysis failed to reveal any significant differences between the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6(+)/NESTIN(+) cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural induction, independent of iPSCs' genetic background. LA - English DB - MTMT ER -