Journal article
Inhibition of TDP-43 accumulation by Bis(thiosemicarbazonato)-copper complexes
SJ Parker, J Meyerowitz, JL James, JR Liddell, T Nonaka, M Hasegawa, KM Kanninen, SC Lim, BM Paterson, PS Donnelly, PJ Crouch, AR White
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2012
Open access
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, motor neuron disease with no effective long-term treatment options. Recently, TDP-43 has been identified as a key protein in the pathogenesis of some cases of ALS. Although the role of TDP-43 in motor neuron degeneration is not yet known, TDP-43 has been shown to accumulate in RNA stress granules (SGs) in cell models and in spinal cord tissue from ALS patients. The SG association may be an early pathological change to TDP-43 metabolism and as such a potential target for therapeutic intervention. Accumulation of TDP-43 in SGs induced by inhibition of mitochondrial activity can be inhibited by modulation of cellular kinase activity. ..
View full abstractGrants
Awarded by Japan Society for the Promotion of Science
Funding Acknowledgements
This work was supported by funding from the National Health and Medical Research Council of Australia and Australian Research Council (ARC). ARW is a recipient of an ARC Future Fellowship Award. PJC is recipient of a C. R. Roper Fellowship. KMK was supported by Sigrid Juselius Foundation, Finland. JLJ was supported by a Rotary Health Scholarship. The authors would also like to thank the Motor Neuron Disease Research Institute of Australia, Bethlehem Griffiths Research Foundation and CASS Foundation for the kind support of this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.