The hypoxia imaging agent Cu ii(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease

Lin Hung, Victor Villemagne, Lesley Cheng, Nicki Sherratt, Scott Ayton, Anthony White, Peter Crouch, Sin Chun Lim, Su Ling Leong, Simon Wilkins, Jessica George, Blaine Roberts, Chi Pham, Xiang Liu, Francis Chiu, David Shackleford, Andrew Powell, Colin Masters, Ashley I Bush, Graeme O'KeefeJanetta Culvenor, Roberto Cappai, Robert Cherny, Paul Donnelly, Andrew Hill, David Finkelstein, Kevin Barnham

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Abstract

Parkinson s disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated a-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration. Hence, we have identified Cu II(atsm) as a potential therapeutic for PD. Drug administration to four different animal models of PD resulted in improved motor and cognition function, rescued nigral cell loss, and improved dopamine metabolism. In vitro, this compound is able to inhibit the effects of peroxynitrite-driven toxicity, including the formation of nitrated a-synuclein oligomers. Our results show that Cu II(atsm) is effective in reversing parkinsonian defects in animal models and has the potential to be a successful treatment of PD.
Original languageEnglish
Pages (from-to)837 - 854
Number of pages18
JournalJournal of Experimental Medicine
Volume209
Issue number4
DOIs
Publication statusPublished - 2012

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