caa a22 4500 445376120 CHVBK 20180317143003.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00702-010-0573-6 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0573-6 Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington's disease [Elektronische Daten] [Dénes Zádori, Gábor Nyiri, András Szőnyi, István Szatmári, Ferenc Fülöp, József Toldi, Tamás Freund, László Vécsei, Péter Klivényi] Huntington's disease (HD) is a progressive neurodegenerative disorder, the pathomechanism of which is not yet fully understood. Excitotoxicity is known to be involved in the development of HD and antiglutamatergic agents may, therefore, have beneficial neuroprotective effects. One of these agents is the tryptophan metabolite kynurenic acid (KYNA), which is an endogenous NMDA receptor antagonist. However, its pharmacological properties rule out its systemic administration in CNS disorders. We have tested a novel KYNA analogue, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride, in the N171-82Q transgenic mouse model of HD. The analogue exhibited several significant effects: it prolonged the survival of the transgenic mice, ameliorated their hypolocomotion, prevented the loss of weight and completely prevented the atrophy of the striatal neurons. The beneficial effects of this KYNA analogue are probably explained by its complex anti-excitotoxic activity. As it did not induce any appreciable side-effect at the protective dose applied in a chronic dosing regime in this mouse model, it appears worthy of further thorough investigations with a view to eventual clinical trials. Springer-Verlag, 2010 Huntington's disease nationallicence Kynurenic acid analogue nationallicence Neuroprotection nationallicence N171-82Q nationallicence Transgenic mice nationallicence Stereology nationallicence Zádori Dénes Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut Nyiri Gábor Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut Szőnyi András Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut Szatmári István Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, 6720, Szeged, Hungary aut Fülöp Ferenc Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, 6720, Szeged, Hungary aut Toldi József Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, 6726, Szeged, Hungary aut Freund Tamás Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut Vécsei László Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut Klivényi Péter Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut Journal of Neural Transmission Springer Vienna 118/6(2011-06-01), 865-875 0300-9564 118:6<865 2011 118 702 https://doi.org/10.1007/s00702-010-0573-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0573-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zádori Dénes Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut NATIONALLICENCE 700 1- Nyiri Gábor Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut NATIONALLICENCE 700 1- Szőnyi András Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut NATIONALLICENCE 700 1- Szatmári István Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Fülöp Ferenc Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, 6720, Szeged, Hungary aut NATIONALLICENCE 700 1- Toldi József Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, 6726, Szeged, Hungary aut NATIONALLICENCE 700 1- Freund Tamás Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083, Budapest, Hungary aut NATIONALLICENCE 700 1- Vécsei László Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut NATIONALLICENCE 700 1- Klivényi Péter Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/6(2011-06-01), 865-875 0300-9564 118:6<865 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer