https://m2.mtmt.hu/ eng 2026-10-24 21:59 JournalArticle 3012667 APPROVED true Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary National Research Council of Italy, Neuroscience Institute, Cagliari, Italy Institute of Chemical Engineering and Science, 8 Biomedical Grove, Neuros, Singapore, 138665, Singapore Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore Institute of Organic Chemistry, Semmelweis University, Budapest, Hungary Cited By :43 Export Date: 18 February 2023 Correspondence Address: Baranyi, M.; Laboratory of Molecular Pharmacology, Hungary; email: baranyi@koki.hu Chemicals/CAS: 1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine, 28289-54-5; dopamine, 51-61-6, 62-31-7; probenecid, 57-66-9; rasagiline, 136236-51-6, 161735-79-1, 1875-50-9; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone), 9028-04-0; rotenone, 83-79-4; tyrosine 3 monooxygenase, 9036-22-0; pargyline, 306-07-0, 555-57-7; propylamine, 107-10-8; Dopamine; dopamine quinone; Pargyline; propargylamine; Propylamines Tradenames: szv 558 Manufacturers: Sigma Aldrich, United States Funding details: 1021490113 Funding details: KTIA_13_NAP-A-III/1 Funding details: TÉT_10-1-2011-0050 Funding details: K116654, NN107234 Funding details: Seventh Framework Programme, FP7, 294313 Funding details: European Research Council, ERC Funding text 1: This study was supported by research grants from the Hungarian Research and Development Fund (Grant NN107234 and K116654 to B.S.), the Hungarian Office of Science and Technology (Grant TÉT_10-1-2011-0050 to B.S.), the European Research Council (Grant 294313-SERRACO to B.S.), Hungarian Brain Research Program [KTIA_13_NAP-A-III/1 to B.S.], Agency for Science Technology and Research, Singapore [grant number 1021490113 to C.L.L.C.]. Dr. Porceddu gratefully acknowledges “the Hungarian Office of Science and Technology” for fellowship support. The authors are grateful for Zsuz-sanna Körössy and Ilona Kéry for expert technical assistance in in vivo experiments, the 3DHISTECH Co., Budapest, Hungary, for the digitalization and quantification of TH staining and Ed Beamer for editing the manuscript. 0 2017-02-21T11:34:42.000+0000 false 3012667 2026-10-17T13:25:43.963+0000 2022-12-04T18:34:12.629+0000 2016-02-03T11:17:44.000+0000 true 10008942 Sperlágh Beáta /api/author/10008942 Author true 10008942 2026-07-02T08:58:23.227+0000 2020-01-28T10:18:22.327+0000 true 10015546 Berhidi Anna /api/admin/10015546 Admin true 10015546 Admin 10066925 /api/admin/10066925 Nemec Évi true true Admin 10067876 /api/admin/10067876 Ladányi Gusztáv true true 2024-10-17T16:20:19.023+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Baranyi, M Novel (Hetero)arylalkenyl propargylamine compounds are protective in toxin-induced models of Parkinson's disease true true /api/journal/10011732 REVIEWED true false 10011732 false 10011732 true 1750-1326 1750-1326 Journal FOREIGN 11 6 6 21 2016 BACKGROUND: Mitochondrial dysfunction, oxidative stress and their interplay are core pathological features of Parkinson's disease. In dopaminergic neurons, monoamines and their metabolites provide an additional source of reactive free radicals during their breakdown by monoamine oxidase or auto-oxidation. Moreover, mitochondrial dysfunction and oxidative stress have a supraadditive impact on the pathological, cytoplasmic accumulation of dopamine and its subsequent release. Here we report the effects of a novel series of potent and selective MAO-B inhibitory (hetero)arylalkenylpropargylamine compounds having protective properties against the supraadditive effect of mitochondrial dysfunction and oxidative stress. RESULTS: The (hetero)arylalkenylpropargylamines were tested in vitro, on acute rat striatal slices, pretreated with the complex I inhibitor rotenone and in vivo, using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced acute, subchronic, and chronic experimental models of Parkinson's disease in mice. The compounds exhibited consistent protective effects against i) in vitro oxidative stress induced pathological dopamine release and the formation of toxic dopamine quinone in the rat striatum and rescued tyrosine hydroxylase positive neurons in the substantia nigra after rotenone treatment; ii) in vivo MPTP-induced striatal dopamine depletion and motor dysfunction in mice using acute and subchronic, delayed application protocols. One compound (SZV558) was also examined and proved to be protective in a chronic mouse model of MPTP plus probenecid (MPTPp) administration, which induces a progressive loss of nigrostriatal dopaminergic neurons. CONCLUSIONS: Simultaneous inhibition of MAO-B and oxidative stress induced pathological dopamine release by the novel propargylamines is protective in animal models and seems a plausible strategy to combat Parkinson's disease. true true 2016 696363 true true true false true false GOLD 2026-10-17 true https://doi.org/10.1186/s13024-015-0067-y true 10020110 Farkas Andrea /api/admin/10020110 Admin true 10020110 69 0 69 61 3 69 69 69 62 69 69 61 61 61 8 0 69 61 69 61 0 8 8 Folyóiratcikk Journal Article 24 69 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 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/api/ratingtype/10002 sjr true true ClassificationExternal 2804 /api/classificationexternal/2804 true 2804 true D1 DIRECT true true /api/publication/3012667 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="91"><a href="/gui2/?type=authors&mode=browse&sel=91" target="_blank">Baranyi M ✉ (<span class="authorship-author-name">Baranyi Mária</span> <span class="authorAux-mtmt"> Molekuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Porceddu PF<sup>*</sup> ✉ </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10052098"><a href="/gui2/?type=authors&mode=browse&sel=10052098" target="_blank">Goloncser F (<span class="authorship-author-name">Gölöncsér Flóra</span> <span class="authorAux-mtmt"> idegtudományok</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology; <span title="Semmelweis University">SU</span>/School of Ph. D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10067089"><a href="/gui2/?type=authors&mode=browse&sel=10067089" target="_blank">Kulcsar S (<span class="authorship-author-name">Kulcsár Szabina</span> <span class="authorAux-mtmt"> ökotoxikológia</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10055678"><a href="/gui2/?type=authors&mode=browse&sel=10055678" target="_blank">Otrokocsi L (<span class="authorship-author-name">Bereczkiné Otrokocsi Lilla</span> <span class="authorAux-mtmt"> élettudomány</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/School of Ph. D. Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009113"><a href="/gui2/?type=authors&mode=browse&sel=10009113" target="_blank">Kittel A (<span class="authorship-author-name">Kittel Ágnes</span> <span class="authorAux-mtmt"> Sejtbiológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Pinna A </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Frau L </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Huleatt PB </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Khoo ML </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Chai CL </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10022042"><a href="/gui2/?type=authors&mode=browse&sel=10022042" target="_blank">Dunkel P (<span class="authorship-author-name">Dunkel Petra</span> <span class="authorAux-mtmt"> Szerves-és gyógyszerkémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Pharmacy">FP</span>/Department of Organic Chemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10007438"><a href="/gui2/?type=authors&mode=browse&sel=10007438" target="_blank">Matyus P (<span class="authorship-author-name">Mátyus Péter</span> <span class="authorAux-mtmt"> Szerves- és gyógyszerkémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Pharmacy">FP</span>/Department of Organic Chemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Morelli M </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10008942"><a href="/gui2/?type=authors&mode=browse&sel=10008942" target="_blank">Sperlagh B (<span class="authorship-author-name">Sperlágh Beáta</span> <span class="authorAux-mtmt"> Neurofarmakológia</span>) </a> </span> <span class="author-affil"><span title="MTA Kísérleti Orvostudományi Kutatóintézet">IEMHAS</span>/<span title="Department of Pharmacology">DP</span>/Laboratory of Molecular Pharmacology</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;3012667" target="_blank">Novel (Hetero)arylalkenyl propargylamine compounds are protective in toxin-induced models of Parkinson's disease</a></div> <div> <span class="journal-title">MOLECULAR NEURODEGENERATION</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1750-1326">1750-1326</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1750-1326">1750-1326</a>)</span>: <span class="journal-volume">11</span> <span class="page"> Paper 6. 21 p. </span> <span class="year">(2016)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1186/s13024-015-0067-y" target="_blank" href="https://doi.org/10.1186/s13024-015-0067-y"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000367911500001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000367911500001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84953790375" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84953790375"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="26758813" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=26758813&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="PMC4711075" target="_blank" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711075"> Pubmed Central </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Cellular and Molecular Neuroscience&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Neurology (clinical)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 69</span> | Independent citation: 61 | Self citation: 8 | Unknown citation: 0 | Number of citations in WoS: 69 | Number of citations in Scopus:&nbsp;62 | WoS/Scopus assigned:&nbsp;69 | Number of citations with DOI:&nbsp;69 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;3012667&sort=publishedYear,desc&sort=title"> Number of cited publications: 8 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 3012667</span> | <span class="status-data status-APPROVED"> Published </span> <span class="oldId">Old id: 3012667</span> | Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="lastModified">Last Modified: 2022.12.04. 19:34 Márta Turek (KOKI admin 4) </div> <div class="lockedBy">Centrally managed 2024.10.17. 18:20 Évi Nemec (MTMT Központi 3, admin) Gusztáv Ladányi (MTMT API user, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary ...</pre> </div></div>