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

The Journal of experimental medicine, 2012-04, Vol.209 (4), p.837-854 [Peer Reviewed Journal]

2012 Hung et al. 2012 ;ISSN: 0022-1007 ;EISSN: 1540-9538 ;DOI: 10.1084/jem.20112285 ;PMID: 22473957

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Title:
The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease
Author: Hung, Lin W ; Villemagne, Victor L ; Cheng, Lesley ; Sherratt, Nicki A ; Ayton, Scott ; White, Anthony R ; Crouch, Peter J ; Lim, SinChun ; Leong, Su Ling ; Wilkins, Simon ; George, Jessica ; Roberts, Blaine R ; Pham, Chi L L ; Liu, Xiang ; Chiu, Francis C K ; Shackleford, David M ; Powell, Andrew K ; Masters, Colin L ; Bush, Ashley I ; O'Keefe, Graeme ; Culvenor, Janetta G ; Cappai, Roberto ; Cherny, Robert A ; Donnelly, Paul S ; Hill, Andrew F ; Finkelstein, David I ; Barnham, Kevin J
Subjects: alpha-Synuclein - chemistry ; Animals ; Cell Line, Tumor ; Cognition - drug effects ; Disease Models, Animal ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Molsidomine - analogs & derivatives ; Molsidomine - pharmacology ; Motor Activity - drug effects ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Organometallic Compounds - pharmacology ; Organometallic Compounds - therapeutic use ; Parkinson Disease - drug therapy ; Parkinson Disease - psychology ; Positron-Emission Tomography ; Radiopharmaceuticals - pharmacology ; Radiopharmaceuticals - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Thiosemicarbazones - pharmacology ; Thiosemicarbazones - therapeutic use
Is Part Of: The Journal of experimental medicine, 2012-04, Vol.209 (4), p.837-854
Description: 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.
Publisher: United States: The Rockefeller University Press
Language: English
Identifier: ISSN: 0022-1007
EISSN: 1540-9538
DOI: 10.1084/jem.20112285
PMID: 22473957
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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

2012 Hung et al. 2012 ;ISSN: 0022-1007 ;EISSN: 1540-9538 ;DOI: 10.1084/jem.20112285 ;PMID: 22473957

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