title: The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease.
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 α-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 α-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.
authors.affiliation: The Mental Health Research Institute, the University of Melbourne, Victoria 3010 Australia.
authors.forename: Lin W
authors.initials: LW
authors.lastname: Hung
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Lesley
authors.initials: L
authors.lastname: Cheng
authors.forename: Nicki A
authors.initials: NA
authors.lastname: Sherratt
authors.forename: Scott
authors.initials: S
authors.lastname: Ayton
authors.forename: Anthony R
authors.initials: AR
authors.lastname: White
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crouch
authors.forename: SinChun
authors.initials: S
authors.lastname: Lim
authors.forename: Su Ling
authors.initials: SL
authors.lastname: Leong
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkins
authors.forename: Jessica
authors.initials: J
authors.lastname: George
authors.forename: Blaine R
authors.initials: BR
authors.lastname: Roberts
authors.forename: Chi L L
authors.initials: CL
authors.lastname: Pham
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Francis C K
authors.initials: FC
authors.lastname: Chiu
authors.forename: David M
authors.initials: DM
authors.lastname: Shackleford
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Powell
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Graeme
authors.initials: G
authors.lastname: O'Keefe
authors.forename: Janetta G
authors.initials: JG
authors.lastname: Culvenor
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003071:Cognition / Q000187:drug effects*; D056831:Coordination Complexes; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013882:Thiosemicarbazones / Q000494:pharmacology / Q000627:therapeutic use*; D051844:alpha-Synuclein / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; D051844:alpha-Synuclein; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C002385:linsidomine; D008981:Molsidomine