@article{MTMT:33068852,
	title = {Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System},
	url = {https://m2.mtmt.hu/api/publication/33068852},
	author = {Tanaka, Masaru and Szabó, Ágnes and Spekker, Eleonóra and Polyák, Helga and Tóth, Fanni and Vécsei, László},
	doi = {10.3390/cells11162607},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {11},
	unique-id = {33068852},
	abstract = {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.},
	keywords = {STRESS; DEPRESSION; Mitochondria; PLASTICITY; KYNURENINE; Alzheimer's disease; anxiety; Psychiatric; STRESS RESILIENCE; Neurodegenerative},
	year = {2022},
	eissn = {2073-4409},
	orcid-numbers = {Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:32153433,
	title = {Co-players in chronic pain : neuroinflammation and the tryptophan-kynurenine metabolic pathway},
	url = {https://m2.mtmt.hu/api/publication/32153433},
	author = {Tanaka, Masaru and Török, Nóra and Tóth, Fanni and Szabó, Ágnes and Vécsei, László},
	doi = {10.3390/biomedicines9080897},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {9},
	unique-id = {32153433},
	year = {2021},
	eissn = {2227-9059},
	orcid-numbers = {Tanaka, Masaru/0000-0003-4383-4024; Török, Nóra/0000-0002-7556-9600; Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:32091772,
	title = {Immune influencers in action : metabolites and enzymes of the tryptophan-kynurenine metabolic pathway},
	url = {https://m2.mtmt.hu/api/publication/32091772},
	author = {Tanaka, Masaru and Tóth, Fanni and Polyák, Helga and Szabó, Ágnes and Mándi, Yvette and Vécsei, László},
	doi = {10.3390/biomedicines9070734},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {9},
	unique-id = {32091772},
	year = {2021},
	eissn = {2227-9059},
	orcid-numbers = {Tanaka, Masaru/0000-0003-4383-4024; Mándi, Yvette/0000-0003-4729-2445; Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:31799016,
	title = {Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid},
	url = {https://m2.mtmt.hu/api/publication/31799016},
	author = {Tóth, Fanni and Cseh, Edina Katalin and Vécsei, László},
	doi = {10.3390/ijms22010403},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {31799016},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:31252898,
	title = {Kinureninek és gyógyszerkutatás [Kynurenines and drug research].},
	url = {https://m2.mtmt.hu/api/publication/31252898},
	author = {Tóth, Fanni and Fülöp, Ferenc and Szatmári, István and Toldi, József and Dékány, Imre and Vécsei, László},
	doi = {10.1556/650.2020.31673},
	journal-iso = {ORV HETIL},
	journal = {ORVOSI HETILAP},
	volume = {161},
	unique-id = {31252898},
	issn = {0030-6002},
	abstract = {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.},
	keywords = {kynurenic acid; neuroprotection; NEURODEGENERATIVE DISEASE; kinurénsav; neurodegenerációs betegség; neuroprotekció},
	year = {2020},
	eissn = {1788-6120},
	pages = {443-451},
	orcid-numbers = {Fülöp, Ferenc/0000-0003-1066-5287; Szatmári, István/0000-0002-8571-5229; Toldi, József/0000-0001-7355-0503; Dékány, Imre/0000-0001-5472-5355; Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:3157890,
	title = {A NOVEL NON-OPIOID BINDING SITE FOR ENDOMORPHIN-1},
	url = {https://m2.mtmt.hu/api/publication/3157890},
	author = {Lengyel, Imre and Tóth, Fanni and Biyashev, Daureen and Szatmári, Ildikó and Monory, K and Tömböly, Csaba and Tóth, Géza and Benyhe, Sándor and Borsodi, Anna},
	journal-iso = {J PHYSIOL PHARMACOL},
	journal = {JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY},
	volume = {67},
	unique-id = {3157890},
	issn = {0867-5910},
	abstract = {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.},
	keywords = {CELLS; RAT-BRAIN; ADENYLYL-CYCLASE; AGONIST; RADIOLIGAND BINDING; MORPHINE; OPIATE RECEPTOR; DELTA; Rat brain; MU-OPIOID-RECEPTOR; KNOCK-OUT MICE; Tritiated endomorphin-1; Naloxone insensitive site; AFFINITY STATES; mu-opioid peptide receptor; G-protein activation},
	year = {2016},
	eissn = {1899-1505},
	pages = {605-616},
	orcid-numbers = {Szatmári, Ildikó/0000-0003-1040-145X}
}

@article{MTMT:3093931,
	title = {Synthesis and binding characteristics of [H-3]neuromedin N, a NTS2 receptor ligand},
	url = {https://m2.mtmt.hu/api/publication/3093931},
	author = {Tóth, Fanni and Mallareddy, Jayapelreddy and Tourwe, D and Lipkowski, AW and Bujalska-Zadrozny, M and Benyhe, Sándor and Ballet, S and Tóth, Géza and Kleczkowska, P},
	doi = {10.1016/j.npep.2015.12.004},
	journal-iso = {NEUROPEPTIDES},
	journal = {NEUROPEPTIDES},
	volume = {57},
	unique-id = {3093931},
	issn = {0143-4179},
	abstract = {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.},
	keywords = {SITES; INACTIVATION; ANTAGONIST; RAT-BRAIN; CLONING; SENSITIVITY; POTENTIATION; aspartate residue; NEUROMEDIN-N; NEUROTENSIN-LIKE PEPTIDE; NTS2; Receptor binding assays; Neuromedin N; rat},
	year = {2016},
	eissn = {1532-2785},
	pages = {15-20}
}

@article{MTMT:2223828,
	title = {Protein kinase C inhibitor BIM suspended TRPV1 effect on mu-opioid receptor},
	url = {https://m2.mtmt.hu/api/publication/2223828},
	author = {Wollemann, Mária and Tóth, Fanni and Benyhe, Sándor},
	doi = {10.1016/j.brainresbull.2012.10.008},
	journal-iso = {BRAIN RES BULL},
	journal = {BRAIN RESEARCH BULLETIN},
	volume = {90},
	unique-id = {2223828},
	issn = {0361-9230},
	abstract = {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.},
	year = {2013},
	eissn = {1873-2747},
	pages = {114-117}
}

@article{MTMT:2110516,
	title = {Opiorphin highly improves the specific binding and affinity of MERF and MEGY to rat brain opioid receptors},
	url = {https://m2.mtmt.hu/api/publication/2110516},
	author = {Tóth, Fanni and Tóth, Géza and Benyhe, Sándor and Rougeot, C and Wollemann, Mária},
	doi = {10.1016/j.regpep.2012.06.011},
	journal-iso = {REGUL PEPTIDES},
	journal = {REGULATORY PEPTIDES},
	volume = {178},
	unique-id = {2110516},
	issn = {0167-0115},
	abstract = {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.},
	year = {2012},
	eissn = {1873-1686},
	pages = {71-75}
}

@article{MTMT:2057817,
	title = {Radiotracers, tritium labelling of neuropeptides},
	url = {https://m2.mtmt.hu/api/publication/2057817},
	author = {Tóth, Géza and Mallareddy, Jayapelreddy and Tóth, Fanni and Lipkowski, AW and Tourwe, D},
	doi = {10.3998/ark.5550190.0013.515},
	journal-iso = {ARKIVOC},
	journal = {ARKIVOC},
	volume = {2012},
	unique-id = {2057817},
	issn = {1551-7012},
	year = {2012},
	eissn = {1551-7004},
	pages = {163-174}
}