Oral treatment with CuII(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis

BR Roberts; NKH Lim; EJ McAllum; PS Donnelly; DJ Hare; PA Doble; BJ Turner; KA Price; SC Lim; BM Paterson; JL Hickey; TW Rhoads; JR Williams; KM Kanninen; LW Hung; JR Liddell; A Grubman; JF Monty; RM Llanos; DR Kramer; JFB Mercer; AI Bush; CL Masters; JA Duce; QX Li; JS Beckman; KJ Barnham; AR White; PJ Crouch

Journal article

Oral treatment with CuII(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis

BR Roberts, NKH Lim, EJ McAllum, PS Donnelly, DJ Hare, PA Doble, BJ Turner, KA Price, SC Lim, BM Paterson, JL Hickey, TW Rhoads, JR Williams, KM Kanninen, LW Hung, JR Liddell, A Grubman, JF Monty, RM Llanos, DR Kramer Show all

Journal of Neuroscience | Published : 2014

DOI: 10.1523/JNEUROSCI.4196-13.2014

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Abstract

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copperII [CuII(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with CuII(a..

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University of Melbourne Researchers

Paul Donnelly Author

Dominic Hare Author

Bradley Turner Author

Jeffrey Liddell Author

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Awarded by Australian National Health and Medical Research Council

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by funds from the Australian National Health and Medical Research Council (Project Grants 1005651 and 1061550); the Motor Neuron Disease Research Institute of Australia; the Victorian Government Operational Infrastructure Support Program; Bethlehem Griffiths Research Foundation; the CASS Foundation; the Australian Research Council; the National Academy of Finland; the Sigrid Juselius Foundation; and The University of Melbourne.