The dopaminergic stabilizer, (-)-OSU6162, rescues striatal neurons with normal and expanded polyglutamine chains in huntingtin protein from exposure to free radicals and mitochondrial toxins

Brain Research
Carolina RuízJusto García de Yebenes

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

Jan 1, 1997·Journal of Neural Transmission·M A MenaJ García de Yébenes
Nov 25, 2000·Human Molecular Genetics·F TrettelM E MacDonald
Aug 14, 2003·Human Molecular Genetics·Jean-Michel ItierJusto Garcia de Yebenes
Feb 18, 2004·Current Medicinal Chemistry·M L CarlssonM Nilsson
May 26, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Johan P RungMaria L Carlsson
Dec 13, 2006·European Journal of Pharmacology·Philip Seeman, Hong-Chang Guan
Jul 30, 2010·European Journal of Pharmacology·Henrik PontenNicholas Waters
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading
Jun 29, 2011·Molecular and Cellular Neurosciences·Carla NunesJoão Laranjinha
Aug 30, 2011·Journal of Neural Transmission·Maria L CarlssonArvid Carlsson

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Citations

Aug 21, 2013·Cell Death & Disease·J SassoneA Ciammola
Oct 14, 2014·BioMed Research International·Jonasz Jeremiasz WeberJeannette Hübener

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