TY - JOUR AU - Tanaka, Masaru AU - Szabó, Ágnes AU - Spekker, Eleonóra AU - Polyák, Helga AU - Tóth, Fanni AU - Vécsei, László TI - Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System JF - CELLS J2 - CELLS-BASEL VL - 11 PY - 2022 IS - 16 PG - 42 SN - 2073-4409 DO - 10.3390/cells11162607 UR - https://m2.mtmt.hu/api/publication/33068852 ID - 33068852 N1 - ELKH-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Tisza Lajos krt. 113, Szeged, H-6725, Hungary Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary School of Clinical Medicine, University of Szeged, Korányi fasor 6, Szeged, H-6720, Hungary Cited By :95 Export Date: 6 March 2024 Correspondence Address: Vécsei, L.; ELKH-SZTE Neuroscience Research Group, Tisza Lajos krt. 113, Hungary; email: vecsei.laszlo@med.u-szeged.hu Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 138125, MTA-JSP-050609 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, EFOP-3.6.3-VEKOP-16-2017-00009, ÚNKP-21-3 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: This research was funded by National Research, Development and Innovation Office – NKFIH 138125, MTA-JSP-050609, and ELKH-SZTE. Helga Polyák was supported by the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research Development and Innovation Fund [ÚNKP-21-3] and EFOP-3.6.3-VEKOP-16-2017-00009. AB - Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases. LA - English DB - MTMT ER - TY - JOUR AU - Tanaka, Masaru AU - Török, Nóra AU - Tóth, Fanni AU - Szabó, Ágnes AU - Vécsei, László TI - Co-players in chronic pain : neuroinflammation and the tryptophan-kynurenine metabolic pathway JF - BIOMEDICINES J2 - BIOMEDICINES VL - 9 PY - 2021 IS - 8 PG - 18 SN - 2227-9059 DO - 10.3390/biomedicines9080897 UR - https://m2.mtmt.hu/api/publication/32153433 ID - 32153433 N1 - Funding Agency and Grant Number: University of Szeged [4942]; [GINOP 2.3.2-15-2016-00034]; [GINOP 2.3.2-15-2016-00048]; [TUDFO/47138-1/2019-ITM] Funding text: This research was funded by GINOP 2.3.2-15-2016-00034, GINOP 2.3.2-15-2016-00048, TUDFO/47138-1/2019-ITM, and TKP2020 Thematic Excellence Programme 2020-The APC was funded by the University of Szeged Open Access Fund (4942). LA - English DB - MTMT ER - TY - JOUR AU - Tanaka, Masaru AU - Tóth, Fanni AU - Polyák, Helga AU - Szabó, Ágnes AU - Mándi, Yvette AU - Vécsei, László TI - Immune influencers in action : metabolites and enzymes of the tryptophan-kynurenine metabolic pathway JF - BIOMEDICINES J2 - BIOMEDICINES VL - 9 PY - 2021 IS - 7 PG - 23 SN - 2227-9059 DO - 10.3390/biomedicines9070734 UR - https://m2.mtmt.hu/api/publication/32091772 ID - 32091772 N1 - MTA-SZTE—Neuroscience Research Group, Szeged, H-6725, Hungary Interdisciplinary Excellence Centre, Department of Neurology, Faculty of Medicine, University of Szeged, Szeged, H-6725, Hungary Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Szeged, Szeged, H-6720, Hungary Cited By :115 Export Date: 24 October 2023 Correspondence Address: Vécsei, L.; MTA-SZTE—Neuroscience Research GroupHungary; email: vecsei.laszlo@med.u-szeged.hu Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, EFOP 3.6.3-VEKOP-16-2017-00009 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: Funding: This research was funded by GINOP 2.3.2-15-2016-00034, GINOP 2.3.2-15-2016-00048, TUDFO/47138-1/2019-ITM and TKP2020 Thematic Excellence Programme 2020. Helga Polyák was supported by the ÚNKP-20-3—New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund; and EFOP 3.6.3-VEKOP-16-2017-00009. The APC was funded by University of Szeged Open Access Fund (4942). LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Fanni AU - Cseh, Edina Katalin AU - Vécsei, László TI - Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 1 PG - 25 SN - 1661-6596 DO - 10.3390/ijms22010403 UR - https://m2.mtmt.hu/api/publication/31799016 ID - 31799016 N1 - Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine University of Szeged, Semmelweis Street 6, Szeged, H-6725, Hungary MTA-SZTE, Neuroscience Research Group, Semmelweis Street 6, Szeged, H-6725, Hungary Cited By :28 Export Date: 11 September 2023 Correspondence Address: Vécsei, L.; Department of Neurology, Semmelweis Street 6, Hungary; email: vecsei.laszlo@med.u-szeged.hu Correspondence Address: Vécsei, L.; MTA-SZTE, Semmelweis Street 6, Hungary; email: vecsei.laszlo@med.u-szeged.hu Chemicals/CAS: kynurenic acid, 492-27-3; kynurenine, 16055-80-4, 343-65-7; kynurenine aminotransferase, 9030-38-0; pantethine, 16816-67-4; pantothenate kinase, 9026-48-6; thioctic acid, 1077-29-8, 2319-84-8, 62-46-4; tryptophan, 6912-86-3, 73-22-3; pantetheine, 496-65-1; Antioxidants; Kynurenic Acid; Neuroprotective Agents; Pantetheine; pantethine; Thioctic Acid Funding details: 2.3.2-15-2016-00034, NKFIH-1279-2/2020 TKP 2020 Funding details: 5043 Funding details: Szegedi Tudományegyetem, SZTE Funding text 1: Acknowledgments: We would like to thank the University of Szeged Institutional Open Access Program for funding the article processing charge. Funding text 2: Funding: This research was funded by GINOP 2.3.2-15-2016-00034, NKFIH-1279-2/2020 TKP 2020 Thematic Excellence Programme and University of Szeged Open Access Fund, Grant number 5043. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Fanni AU - Fülöp, Ferenc AU - Szatmári, István AU - Toldi, József AU - Dékány, Imre AU - Vécsei, László TI - Kinureninek és gyógyszerkutatás [Kynurenines and drug research]. JF - ORVOSI HETILAP J2 - ORV HETIL VL - 161 PY - 2020 IS - 12 SP - 443 EP - 451 PG - 9 SN - 0030-6002 DO - 10.1556/650.2020.31673 UR - https://m2.mtmt.hu/api/publication/31252898 ID - 31252898 N1 - Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Interdiszciplináris Kiválósági Központ, Neurológiai Klinika, Szeged, Hungary MTA-SZTE, Idegtudományi Kutatócsoport, Szeged, Hungary Szegedi Tudományegyetem, Gyógyszerésztudományi Kar, Interdiszciplináris Kiválósági Központ, Gyógyszerkémiai Intézet, Szeged, Hungary MTA-SZTE, Sztereokémiai Kutatócsoport, Szeged, Hungary Szegedi Tudományegyetem, Természettudományi és Informatikai Kar, Biológia Intézet, Élettani, Szervezettani és Idegtudományi Tanszék, Szeged, Hungary Szegedi Tudományegyetem, Természettudományi és Informatikai Kar, Interdiszciplináris Kiválósági Központ, Kémiai Intézet, Fizikai Kémiai és Anyagtudományi Tanszék, Szeged, Hungary MTA-SZTE, Biomimetikus Rendszerek Kutatócsoport, Szeged, Hungary Export Date: 7 March 2024 CODEN: ORHEA Correspondence Address: Vécsei, L.Semmelweis u. 6, Hungary; email: vecsei.laszlo@med.u-szeged.hu AB - Currently kynurenines are considered a hot topic, because of their involvement in numerous physiological and pathological processes. The essential amino acid, tryptophan's main metabolism is through the kynurenine pathway. During the degradation of tryptophan, kynurenic acid is formed with the help of kynurenine aminotransferases. Kynurenic acid is an excitatory receptor ligand and it possesses neuroprotective properties. Abnormal decrease or increase in the kynurenic acid level can cause an imbalance in the neurotransmitter systems and it is associated with several neurodegenerative and neuropsychiatric disorders. Kynurenic acid has a poor penetration through the blood-brain barrier, so it is unfit for therapeutic purposes. For this reason, the aim of our research was the synthesis and pharmacological testing of kynurenic acid analogues with a better blood-brain barrier penetration. The newly synthetized kynurenic acid analogues proved to be effective in models of some nervous system disorders (migraine, Huntington's disease). According to our results with the novel kynurenic acid analogues, these molecules may represent a new therapeutic target in the treatment of neurodegenerative diseases. Several patent applications were filed based on our results. Orv Hetil. 2020; 161(12): 443-451. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Lengyel, Imre AU - Tóth, Fanni AU - Biyashev, Daureen AU - Szatmári, Ildikó AU - Monory, K AU - Tömböly, Csaba AU - Tóth, Géza AU - Benyhe, Sándor AU - Borsodi, Anna TI - A NOVEL NON-OPIOID BINDING SITE FOR ENDOMORPHIN-1 JF - JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - J PHYSIOL PHARMACOL VL - 67 PY - 2016 IS - 4 SP - 605 EP - 616 PG - 12 SN - 0867-5910 UR - https://m2.mtmt.hu/api/publication/3157890 ID - 3157890 N1 - Cited By :8 Export Date: 22 June 2022 CODEN: JPHPE AB - Endomorphins are natural amidated opioid tetrapeptides with the following structure: Tyr-Pro-Trp-Phe-NH2 (endomorphin-1), and Tyr-Pro-Phe-Phe-NH2 (endomorphin-2). Endomorphins interact selectively with the mu-opioid or MOP receptors and exhibit nanomolar or sub-nanomolar receptor binding affinities, therefore they suggested to be endogenous agonists for the mu-pioid receptors. Endomorphins mediate a number of characteristic opioid effects, such as antinociception, however there are several physiological functions in which endomorphins appear to act in a fashion that does not involve binding to and activation of the mu-opioid receptor. Our recent data indicate that a radiolabelled [H-3]endomorphin-1 with a specific radioactivity of 2.35 TBq/mmol -prepared by catalytic dehalogenation of the diiodinated peptide precursor in the presence of tritium gas-is able to bind to a second, naloxone insensitive recognition site in rat brain membranes. Binding heterogeneity, i.e., the presence of higher (K-d = 0.4 nM /B-max = 120 fmol/mg protein) and lower (K-d = 8.2 nM /B-max,, = 432 fmol/mg protein) affinity binding components is observed both in saturation binding experiments followed by Schatchard analysis, and in equilibrium competition binding studies. The signs of receptor multiplicity, e.g., curvilinear Schatchard plots or biphasic displacement curves are seen only if the nonspecific binding is measured in the presence of excess unlabeled endomorphin-1 and not in the presence of excess unlabeled naloxone. The second, lower affinity non-opioid binding site is not recognized by heterocyclic opioid alkaloid ligands, neither agonists such as morphine, nor antagonists such as naloxone. On the contrary, endomorphin-1 is displaced from its lower affinity, higher capacity binding site by several natural neuropeptides, including methionine-enkephalin-Arg-Phe, nociceptin-orphanin FQ, angiotensin and FMRF-amide. This naloxone-insensitive, consequently non-opioid binding site seems to be present in nervous tissues carrying low density or no mu-opioid receptors, such as rodent cerebellum, or brain of mu-opioid receptor deficient (MOPr-/-) transgenic or 'knock-out' (K.O.) mice. The newly described non-opioid binding component is not coupled to regulatory G-proteins, nor does it affect adenylyl cyclase enzyme activity. Taken together endomorphin-1 carries opioid and, in addition to non-opioid functions that needs to be taken into account when various effects of endomorphin-1 are evaluated in physiological or pathologic conditions. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Fanni AU - Mallareddy, Jayapelreddy AU - Tourwe, D AU - Lipkowski, AW AU - Bujalska-Zadrozny, M AU - Benyhe, Sándor AU - Ballet, S AU - Tóth, Géza AU - Kleczkowska, P TI - Synthesis and binding characteristics of [H-3]neuromedin N, a NTS2 receptor ligand JF - NEUROPEPTIDES J2 - NEUROPEPTIDES VL - 57 PY - 2016 SP - 15 EP - 20 PG - 6 SN - 0143-4179 DO - 10.1016/j.npep.2015.12.004 UR - https://m2.mtmt.hu/api/publication/3093931 ID - 3093931 N1 - : LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND AB - Neurotensin (NT) and its analog neuromedin N (NN) are formed by the processing of a common precursor in mammalian brain tissue and intestines. The biological effects mediated by NT and NN (e.g. analgesia, hypothermia) result from the interaction with G protein-coupled receptors. The goal of this study consisted of the synthesis and radiolabeling of NN, as well as the determination of the binding characteristics of [H-3]NN and G protein activation by the cold ligand. In homologous displacement studies a weak affinity was determined for NN, with IC50 values of 454 nM in rat brain and 425 nM in rat spinal cord membranes. In saturation binding experiments the Kd value proved to be 264.8 +/- 30.18 nM, while the B-max value corresponded to 3.8 02 pmol/mg protein in rat brain membranes. The specific binding of [H-3]NN was saturable, interacting with a single set of homogenous binding sites. In sodium sensitivity experiments, a very weak inhibitory effect of Na+ ions was observed on the binding of resulting in an IC50 of 150.6 inM. In [S-35]GTP gamma S binding experiments the E-max value was 112.3 +/- 1.4% in rat brain and 112.9 +/- 2.4% in rat spinal cord membranes and EC50 values of 0.7 nM and 0.79 nM were determined, respectively. NN showed moderate agonist activities in stimulating G proteins. The stimulatory effect of NN could be maximally inhibited via use of the NTS2 receptor antagonist levocabastine, but not by the opioid receptor specific antagonist naloxone, nor by the NTS1 antagonist SR48692. These observations allow us to conclude that [H-3]NN labels NTS2 receptors in rat brain membranes. (C) 2015 Elsevier Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Wollemann, Mária AU - Tóth, Fanni AU - Benyhe, Sándor TI - Protein kinase C inhibitor BIM suspended TRPV1 effect on mu-opioid receptor JF - BRAIN RESEARCH BULLETIN J2 - BRAIN RES BULL VL - 90 PY - 2013 SP - 114 EP - 117 PG - 4 SN - 0361-9230 DO - 10.1016/j.brainresbull.2012.10.008 UR - https://m2.mtmt.hu/api/publication/2223828 ID - 2223828 N1 - Funding Agency and Grant Number: Hungarian Research Foundation (OTKA)Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [CK 78566] Funding text: The study was supported by a grant from the Hungarian Research Foundation (OTKA) CK 78566. The authors wish to thank Mrs. Katalin Horvath Pappne for her excellent technical assistance. Export Date: 17 August 2020 CODEN: BRBUD AB - The purpose of the present study was to elucidate the role of protein kinase A and C in the mechanism of capsaicin inhibition on mu-opiate receptors. H89, a protein kinase A inhibitor and BIM (bisindolylmaleimide), a protein kinase C inhibitor were used for this purpose. BIM suspended the inhibition of capsaicin in endomorphin-1 competition binding. The addition of BIM alone had no effect itself on this reaction. H89 however, exerted a strong inhibitory effect on the endomorphin-1 binding. We can conclude that protein kinase C certainly plays a role in the inhibition of capsaicin. The role of protein kinase A in this reaction could not be established, owing to the blocking effect of H89 on the mu-opioid receptors. (c) 2012 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Fanni AU - Tóth, Géza AU - Benyhe, Sándor AU - Rougeot, C AU - Wollemann, Mária TI - Opiorphin highly improves the specific binding and affinity of MERF and MEGY to rat brain opioid receptors JF - REGULATORY PEPTIDES J2 - REGUL PEPTIDES VL - 178 PY - 2012 IS - 1-3 SP - 71 EP - 75 PG - 5 SN - 0167-0115 DO - 10.1016/j.regpep.2012.06.011 UR - https://m2.mtmt.hu/api/publication/2110516 ID - 2110516 AB - Endogenously occurring opioid peptides are rapidly metabolized by different ectopeptidases. Human opiorphin is a recently discovered natural inhibitor of the enkephalin-inactivating neutral endopeptidase (NEP) and aminopeptidase-N (AP-N) (Wisner et al., 2006). To date, in vitro receptor binding experiments must be performed either in the presence of a mixture of peptidase inhibitors and/or at low temperatures, to block peptidase activity. Here we demonstrate that, compared to classic inhibitor cocktails, opiorphin dramatically increases the binding of [H-3]MERF and [H-3]MEGY ligands to rat brain membrane preparations. We found that at 0 degrees C the increase in specific binding is as high as 40-60% and at 24 degrees C this rise was even higher. In contrast, the binding of the control [H-3]endomorphin-1, which is relatively slowly degraded in rat brain membrane preparations, was not enhanced by opiorphin compared to other inhibitors. In addition, in homologous binding displacement experiments, the IC50 affinity values measured at 24 degrees C were also significantly improved using opiorphin compared to the inhibitor cocktail. In heterologous binding experiments the differences were less obvious, but still pronounced using [H-3]MERF and MEGY compared to dynorphin(1-11), or naloxone and DAGO competitor ligands. (C) 2012 Elsevier B.V. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Géza AU - Mallareddy, Jayapelreddy AU - Tóth, Fanni AU - Lipkowski, AW AU - Tourwe, D TI - Radiotracers, tritium labelling of neuropeptides JF - ARKIVOC J2 - ARKIVOC VL - 2012 PY - 2012 SP - 163 EP - 174 PG - 12 SN - 1551-7012 DO - 10.3998/ark.5550190.0013.515 UR - https://m2.mtmt.hu/api/publication/2057817 ID - 2057817 N1 - Megjegyzés-23433468 PN 5 WoS:hiba:000308697400015 2019-03-03 19:47 kötet nem egyezik LA - English DB - MTMT ER -