Journal article

Mutant TDP-43 Deregulates AMPK Activation by PP2A in ALS Models

ND Perera, RK Sheean, JW Scott, BE Kemp, MK Horne, BJ Turner

PLoS One | Europe PubMed Central | Published : 2014


Bioenergetic abnormalities and metabolic dysfunctionoccur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models. However, whether metabolic dysfunction occurs earlyin ALS pathophysiology linked to different ALS genes remains unclear.Here, we investigatedAMP-activated protein kinase (AMPK) activation, which is a key enzyme induced by energy depletion and metabolic stress, inneuronal cells and mouse models expressing mutantsuperoxide dismutase 1 (SOD1)or TAR DNA binding protein 43 (TDP-43) linked to ALS.AMPKphosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated incytoplasmic granules in motor neurons, but not in pre..

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Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

This work was supported by the Australian National Health and Medical Research Council (Project Grant 1008910), MND Research Institute of Australia (Mick Rodger Benalla and Susie Harris Memorial Fund MND Research Grants), Bethlehem Griffiths Research Foundation and Victorian Government through the Operational Infrastructure Scheme. N.P. is supported by an Australian Postgraduate Award Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.