Abstract
Huntington's disease (HD) is a neurodegenerative disease characterized by progressive motor, cognitive and psychiatric deficits, associated with predominant loss of striatal neurons and caused by a polyglutamine expansion in the huntingtin protein. There is so far neither cure nor approved disease-slowing therapy for HD, though recent clinical studies have shown a beneficial long-term effect of pridopidine in patients with HD. The nature of this effect, purely symptomatic or, in addition, neuroprotective, is difficult to elucidate in clinical trials. Pridopidine and (-)-OSU6162 are members of a new family of compounds referred to as dopaminergic stabilizers, which normalize abnormal dopamine neurotransmission. We investigated the effects of (-)-OSU6162 on huntingtin knocked-in striatal neurons in culture. Control neurons had normal full-length huntingtin with 7 glutamines while "mutant" neurons had large expansions (Q=111). We studied the dose-effect curves of (-)-OSU6162 on mitochondrial activity, LDH levels, necrosis and apoptosis in untreated Q7 and Q111 cells. In addition, we investigated the effects of (-)-OSU6162 on Q7 and Q111 neurons challenged with different neurotoxins such as sodium glutamate, H(2)O(2), rotenone and ...Continue Reading
References
Mar 1, 1969·Analytical Biochemistry·F Tietze
Aug 19, 1994·Journal of Medicinal Chemistry·C SonessonH Wikström
Apr 1, 1993·Neuroreport·M A MenaJ G De Yebenes
Jan 31, 1996·Neuroreport·M A MenaJ García de Yébenes
Jan 1, 1997·Journal of Neural Transmission·M A MenaJ García de Yébenes
May 1, 1997·Brain Research. Brain Research Protocols·B PardoM A Mena
Oct 26, 1999·Neurology·J TedroffA Carlsson
Nov 25, 2000·Human Molecular Genetics·F TrettelM E MacDonald
May 8, 2001·Neuroreport·E Küppers, C Beyer
Aug 14, 2003·Human Molecular Genetics·Jean-Michel ItierJusto Garcia de Yebenes
Feb 18, 2004·Current Medicinal Chemistry·M L CarlssonM Nilsson
Jan 22, 2005·Journal of Neurochemistry·Esther Pérez-NavarroJordi Alberch
May 26, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Johan P RungMaria L Carlsson
Jul 8, 2005·Journal of Neurochemistry·M J CasarejosM A Mena
Dec 13, 2006·European Journal of Pharmacology·Philip Seeman, Hong-Chang Guan
Jul 7, 2007·Journal of Neural Transmission·R A LahtiA Carlsson
Mar 21, 2008·Journal of Neural Transmission·Johan P RungMaria L Carlsson
Jun 25, 2009·Journal of Neurochemistry·Maria J CasarejosMaria A Mena
Jul 10, 2009·Synapse·Philip SeemanKeiji Miyata
Jul 30, 2010·European Journal of Pharmacology·Henrik PontenNicholas Waters
Sep 2, 2010·British Journal of Pharmacology·Elodie KaraPhilip G Strange
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading
Jun 29, 2011·Molecular and Cellular Neurosciences·Carla NunesJoão Laranjinha
Aug 26, 2011·Journal of Neural Transmission·Ethan S BursteinUli Hacksell
Aug 30, 2011·Journal of Neural Transmission·Maria L CarlssonArvid Carlsson
Nov 11, 2011·Lancet Neurology·Justo Garcia de YebenesUNKNOWN MermaiHD study investigators
Citations
Aug 21, 2013·Cell Death & Disease·J SassoneA Ciammola
Sep 23, 2014·Acta Neuropsychiatrica·Angelica KlobergSara Haghighi
Jul 15, 2015·Psychopharmacology·Kristoffer SahlholmAren van Waarde
Oct 14, 2014·BioMed Research International·Jonasz Jeremiasz WeberJeannette Hübener
Jun 23, 2015·Journal of Cellular and Molecular Medicine·Ferdinando SquitieriLuigi Frati