@article{MTMT:34030642, title = {Alzheimer-kór: le tudjuk-e lassítani a betegséget, lesz-e oki terápia?}, url = {https://m2.mtmt.hu/api/publication/34030642}, author = {Penke, Botond and Szűcs, Mária and Bogár, Ferenc}, journal-iso = {BIOKÉMIA}, journal = {BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA}, volume = {47}, unique-id = {34030642}, issn = {0133-8455}, year = {2023}, eissn = {2060-8152}, pages = {10-29}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Bogár, Ferenc/0000-0002-0611-1452} } @article{MTMT:33773509, title = {A 80 éves Penke Botond köszöntése}, url = {https://m2.mtmt.hu/api/publication/33773509}, author = {Szűcs, Mária and Tóth, Gábor}, journal-iso = {MAGY KEM LAP}, journal = {MAGYAR KÉMIKUSOK LAPJA}, volume = {78}, unique-id = {33773509}, issn = {0025-0163}, year = {2023}, eissn = {1588-1199}, pages = {95} } @article{MTMT:33702944, title = {New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease}, url = {https://m2.mtmt.hu/api/publication/33702944}, author = {Penke, Botond and Szűcs, Mária and Bogár, Ferenc}, doi = {10.3390/ijms24065383}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33702944}, issn = {1661-6596}, abstract = {Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disorder. AD is a complex and multifactorial disease that is responsible for 60–80% of dementia cases. Aging, genetic factors, and epigenetic changes are the main risk factors for AD. Two aggregation-prone proteins play a decisive role in AD pathogenesis: β-amyloid (Aβ) and hyperphosphorylated tau (pTau). Both of them form deposits and diffusible toxic aggregates in the brain. These proteins are the biomarkers of AD. Different hypotheses have tried to explain AD pathogenesis and served as platforms for AD drug research. Experiments demonstrated that both Aβ and pTau might start neurodegenerative processes and are necessary for cognitive decline. The two pathologies act in synergy. Inhibition of the formation of toxic Aβ and pTau aggregates has been an old drug target. Recently, successful Aβ clearance by monoclonal antibodies has raised new hopes for AD treatments if the disease is detected at early stages. More recently, novel targets, e.g., improvements in amyloid clearance from the brain, application of small heat shock proteins (Hsps), modulation of chronic neuroinflammation by different receptor ligands, modulation of microglial phagocytosis, and increase in myelination have been revealed in AD research.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Bogár, Ferenc/0000-0002-0611-1452} } @article{MTMT:31277461, title = {Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis}, url = {https://m2.mtmt.hu/api/publication/31277461}, author = {Penke, Botond and Szűcs, Mária and Bogár, Ferenc}, doi = {10.3390/molecules25071659}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {25}, unique-id = {31277461}, issn = {1420-3049}, year = {2020}, eissn = {1420-3049}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Bogár, Ferenc/0000-0002-0611-1452} } @article{MTMT:3315334, title = {The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases}, url = {https://m2.mtmt.hu/api/publication/3315334}, author = {Penke, Botond and Fülöp, Lívia and Szűcs, Mária and Frecska, Ede}, doi = {10.2174/1570159X15666170529104323}, journal-iso = {CURR NEUROPHARMACOL}, journal = {CURRENT NEUROPHARMACOLOGY}, volume = {16}, unique-id = {3315334}, issn = {1570-159X}, abstract = {Background: Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death. Methods: Research articles on Sigma-1 receptor were reviewed. Results: ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins. Conclusion: Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.}, keywords = {ANTAGONIST; RAT-BRAIN; ALZHEIMERS-DISEASE; IN-VITRO; PHARMACOLOGY; AGONIST; LIGAND-BINDING; HIGH-AFFINITY BINDING; ENDOPLASMIC-RETICULUM; neurodegenerative diseases; chaperone; TRAUMATIC BRAIN-INJURY; AMYOTROPHIC-LATERAL-SCLEROSIS; Unfolded protein response; Sigma-1 receptor; STEROL C-8-C-7 ISOMERASE; DMT}, year = {2018}, eissn = {1875-6190}, pages = {97-116}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Fülöp, Lívia/0000-0002-8010-0129} } @article{MTMT:2486869, title = {Ligand-Specific Regulation of the Endogenous Mu-Opioid Receptor by Chronic Treatment with Mu-Opioid Peptide Agonists}, url = {https://m2.mtmt.hu/api/publication/2486869}, author = {Muranyi, M and Cinar, Resat and Kékesi, Orsolya Sára and Birkás, Erika and Fábián, Gabriella and Bozó, Bea and Zentai, A and Tóth, Géza and Kicsi, EG and Macsai, M and Dochnal, Roberta and Szabó, Gyula and Szűcs, Mária}, doi = {10.1155/2013/501086}, journal-iso = {BIOMED RES INT}, journal = {BIOMED RESEARCH INTERNATIONAL}, volume = {2013}, unique-id = {2486869}, issn = {2314-6133}, abstract = {Since the discovery of the endomorphins (EM), the postulated endogenous peptide agonists of the mu-opioid receptors, several analogues have been synthesized to improve their binding and pharmacological profiles. We have shown previously that a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid(2)-endomorphin-2 (ACHC-EM2), had elevated mu-receptor affinity, selectivity, and proteolytic stability over the parent compound. In the present work, we have studied its antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2 (45%), which peaked at 10 min after intracerebroventricular (icv) administration in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins in subcellular fractions of rat brain. Also, the density of mu-receptors was upregulated by about 40% in the light membrane fraction, with no detectable changes in surface binding. Distinct receptor regulatory processes were noted in subcellular fractions of rat brains made tolerant by the prototypic full mu-agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These results are discussed in light of the recently discovered phenomenon, that is, the "so-called biased agonism" or "functional selectivity".}, keywords = {IN-VIVO; RAT-BRAIN; DESENSITIZATION; TOLERANCE; MORPHINE; internalization; BIASED AGONISM; FUNCTIONAL SELECTIVITY; BETA-ARRESTIN; G-protein activation}, year = {2013}, eissn = {2314-6141}, orcid-numbers = {Fábián, Gabriella/0000-0002-2323-4948; Szabó, Gyula/0000-0002-3409-5357} } @article{MTMT:2429176, title = {Lack of Regulatory Changes of mu-Opioid Receptors by 14-Methoxymetopon Treatment in Rat Brain. Further Evidence for Functional Selectivity.}, url = {https://m2.mtmt.hu/api/publication/2429176}, author = {Cinar, Resat and Kékesi, Orsolya Sára and Birkás, Erika and Fábián, Gabriella and Schmidhammer, H and Szűcs, Mária}, doi = {10.2174/138161281942140105161245}, journal-iso = {CURR PHARM DESIGN}, journal = {CURRENT PHARMACEUTICAL DESIGN}, volume = {19}, unique-id = {2429176}, issn = {1381-6128}, abstract = {Here we have studied regulatory changes of mu-opioid receptors accompanying in vivo 14-methoxymetopon treatments of rats. Previously, this ligand has been shown to be an extremely potent, centrally acting mu-opioid specific analgesic with low physical dependence, tolerance, respiratory depression, constipation and other side effects. Our work shows that it is a highly potent full agonist of mu-opioid receptor coupled G-protein signaling in vitro, alike the well-known opioid agonist, etorphine. However, unlike etorphine, which desensitized and down-regulated the endogenous mu-opioid receptors, 14-methoxymetopon, given to rats intraperitoneally (i.p.) either acutely or chronically, did not change the binding or G-protein signaling of mu-opioid receptors in rat brain subcellular membranes. Thereby, these data provide further evidence that there is no direct relationship between the efficacy of the ligand in signaling and its ability to internalize or desensitize the receptor. Viewed collectively with published work, it is discussed that mu-opioid receptors display functional selectivity, also called 'biased agonism'. This concept implies that each ligand may induce unique, ligand-specific receptor conformation that can result in distinct agonist-directed trafficking and/or signal transduction pathways associated with the receptor. Ligand-specific signaling may open up new directions for designing potent analgesics that do not interact with unwanted signaling pathways, which mediate undesired side-effects, such as tolerance and dependence.}, year = {2013}, eissn = {1873-4286}, pages = {7348-7354}, orcid-numbers = {Fábián, Gabriella/0000-0002-2323-4948} } @article{MTMT:2217446, title = {Receptor-kutatók kapták a 2012. évi kémiai Nobel-díjat}, url = {https://m2.mtmt.hu/api/publication/2217446}, author = {Szűcs, Mária}, journal-iso = {MAGY KEM LAP}, journal = {MAGYAR KÉMIKUSOK LAPJA}, volume = {68}, unique-id = {2217446}, issn = {0025-0163}, year = {2013}, eissn = {1588-1199}, pages = {39-41} } @article{MTMT:2202294, title = {Intraneuronal β-amyloid and its interactions with proteins and subcellular organelles}, url = {https://m2.mtmt.hu/api/publication/2202294}, author = {Penke, Botond and Toth, AM and Földi, István and Szűcs, Mária and Janáky, Tamás}, doi = {10.1002/elps.201200297}, journal-iso = {ELECTROPHORESIS}, journal = {ELECTROPHORESIS}, volume = {33}, unique-id = {2202294}, issn = {0173-0835}, abstract = {Amyloidogenic aggregation and misfolding of proteins are linked to neurodegeneration. The mechanism of neurodegeneration in Alzheimer's disease, which gives rise to severe neuronal death and memory loss, is not yet fully understood. The amyloid hypothesis remains the most accepted theory for the pathomechanism of the disease. It was suggested that beta-amyloid accumulation may play a key role in initiating the neurodegenerative processes. The recent intracellular beta-amyloid (iA beta) hypothesis emphasizes the primary role of iA beta to initiate the disease by interaction with cytoplasmic proteins and cell organelles, thereby triggering apoptosis. Sophisticated methods (proteomics, protein microarray, and super resolution microscopy) have been used for studying iA beta interactions with proteins and membraneous structures. The present review summarizes the studies on the origin of iA beta and the base of its neurotoxicity: interactions with cytosolic proteins and several cell organelles such as endoplasmic reticulum, endosomes, lysosomes, ribosomes, mitochondria, and the microtubular system.}, keywords = {Humans; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; TAU-PHOSPHORYLATION; PROTEIN INTERACTIONS; ENDOPLASMIC-RETICULUM; Alzheimer's disease; A-BETA; PRECURSOR PROTEIN; proteomics; Neurons/*metabolism/pathology; Proteomics/methods; Organelles/*metabolism; Alzheimer Disease/*metabolism/pathology; Amyloid beta-Peptides/*metabolism; Protein Interaction Maps; NEURODEGENERATIVE DISEASE; INTRACELLULAR ACCUMULATION; MEDIATED CELL-DEATH; 2-DIMENSIONAL GEL-ELECTROPHORESIS; Intraneuronal; ss-Amyloid}, year = {2012}, eissn = {1522-2683}, pages = {3608-3616}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Janáky, Tamás/0000-0002-6466-8283} } @article{MTMT:1868184, title = {Pharmacology of a new tritiated endomorphin-2 analog containing the proline mimetic cis-2-aminocyclohexanecarboxylic acid}, url = {https://m2.mtmt.hu/api/publication/1868184}, author = {Keresztes, Attila and Birkás, Erika and Pahi, A and Tóth, Géza and Bakota, L and Gulya, Károly and Szűcs, Mária}, doi = {10.1016/j.peptides.2011.01.017}, journal-iso = {PEPTIDES}, journal = {PEPTIDES}, volume = {32}, unique-id = {1868184}, issn = {0196-9781}, abstract = {As part of ongoing work aimed at generating proteolytically stable, readily applicable, radiolabeled endomorphin-2 (EM-2) analogs for elucidation of the topological requirements of peptide binding to mu-opioid receptors, we report here on the synthesis, radiolabeling, binding kinetics and binding site distribution of an EM-2 analog in which Pro(2) is replaced by 2-aminocyclohexanecarboxylic acid, ACHC. [H-3][(1S,2R)ACHC](EM)-E-2-2 (specific activity 63.49 Ci x mmol(-1)) bound specifically to its binding sites with high affinity (K-D = 0.55 +/- 0.06 nM) and saturably, yielding a receptor density, B-max of 151 +/- 4 fmol x mg protein(-1) in rat brain membranes. A similar affinity value was obtained in kinetic assays. Both Na+ and Gpp(NH)p decreased the affinity, proving the agonist character of the radioligand. Specific mu-opioid ligands displaced the radioligand with much higher affinities than did delta- and kappa-ligands. The autoradiographic distribution of the binding sites of [H-3][(1S,2R)ACHC](EM)-E-2-2 agreed well with the known locations of the mu-opioid receptors in the rat brain. In consequence of its high affinity, selectivity and enzymatic resistance [19], the new radioligand will be a good tool in studies of the topographical requirements of mu-opioid-specific peptide binding. (C) 2011 Elsevier Inc. All rights reserved.}, year = {2011}, eissn = {1873-5169}, pages = {722-728} }