Journal article

Enhancing survival motor neuron expression extends lifespan and attenuates neurodegeneration in mutant TDP-43 mice

Nirma D Perera, Rebecca K Sheean, Peter J Crouch, Anthony R White, Malcolm K Horne, Bradley J Turner



Defects in the RNA-binding proteins survival motor neuron (SMN) and TAR DNA-binding protein 43 (TDP-43) cause progressive motor neuron degeneration in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), respectively. While low levels of SMN protein in motor neurons result in SMA, recent studies implicate abnormal SMN levels and function in ALS pathogenesis. Here, we determine that SMN protein is upregulated early and progressively in spinal and cortical motor neurons of male transgenic mutant TDP-43A315T mice. Cytoplasmic SMN aggregates that contain TDP-43 and HuR were identified in motor neurons of TDP-43A315T mice, consistent with the incorporation of SMN into stress gra..

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Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

This work was supported by grants from the Australian National Health and Medical Research Council (1008910 and 1104299), Stafford Fox Medical Research Foundation, MND Research Institute of Australia (Mick Rodger MND Research Grant and Ted Dimmick Memorial MND Research Grants), Cure for MND Foundation, Bethlehem Griffiths Research Foundation and Inner Wheel Club of Pakenham. The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. N.D.P. is supported by an Australian Postgraduate Award Scholarship.