Journal article
Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (Cu II(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model
CPW Soon, PS Donnelly, BJ Turner, LW Hung, PJ Crouch, NA Sherratt, JL Tan, NKH Lim, L Lam, L Bica, SC Lim, JL Hickey, J Morizzi, A Powell, DI Finkelstein, JG Culvenor, CL Masters, J Duce, AR White, KJ Barnham Show all
Journal of Biological Chemistry | Published : 2011
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)- methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical c..
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Grants
Awarded by C. J. Martin Fellowship
Funding Acknowledgements
This work was supported by the Australian National Health and Medical Research Council (NHMRC), C. J. Martin Fellowship 359269 (to B. J. T.), the Bethlehem Griffiths Research Foundation, the Motor Neurone Disease Research Institute of Australia, and the Australian Research Council.