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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.

Authors :
Hung LW
Villemagne VL
Cheng L
Sherratt NA
Ayton S
White AR
Crouch PJ
Lim S
Leong SL
Wilkins S
George J
Roberts BR
Pham CL
Liu X
Chiu FC
Shackleford DM
Powell AK
Masters CL
Bush AI
O'Keefe G
Culvenor JG
Cappai R
Cherny RA
Donnelly PS
Hill AF
Finkelstein DI
Barnham KJ
Source :
The Journal of experimental medicine [J Exp Med] 2012 Apr 09; Vol. 209 (4), pp. 837-54. Date of Electronic Publication: 2012 Apr 02.
Publication Year :
2012

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.

Details

Language :
English
ISSN :
1540-9538
Volume :
209
Issue :
4
Database :
MEDLINE
Journal :
The Journal of experimental medicine
Publication Type :
Academic Journal
Accession number :
22473957
Full Text :
https://doi.org/10.1084/jem.20112285