Survival motor neuron loss in motor neuron disease

Grant number: 1008910 | Funding period: 2011 - 2014

Completed

Abstract

The aim of this proposal is to understand the earliest and central pathological events in motor neuron disease (MND). This is important for drug development because therapies that target the early disease stages are likely to be effective. Our previous studies suggest that a protein essential for nerve cells, survival motor neuron, is lacking in MND. We will therefore examine how early this deficiency starts in disease and whether its replacement is beneficial. These outcomes may aid future studies to design new treatments for MND.

Related publications (12)

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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

2016-09-15

Defects in the RNA-binding proteins survival motor neuron (SMN) and TAR DNA-binding protein 43 (TDP-43) cause progressive motor ne..

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AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral Sclerosis

Nirma D Perera, Bradley J Turner

2016-03-01

Amyotrophic lateral sclerosis (ALS) is caused by selective loss of upper and lower motor neurons by complex mechanisms that are in..

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Effect of thymic stimulation of CD4 T cell expansion on disease onset and progression in mutant SOD1 mice.

RK Sheean, RH Weston, ND Perera, A D'Amico, SL Nutt, BJ Turner

2015-12-01

The peripheral immune system is implicated in modulating microglial activation, neurodegeneration and disease progression in amyot..

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SOD1 protein aggregates stimulate macropinocytosis in neurons to facilitate their propagation

Rafaa Zeineddine, Jay F Pundavela, Lisa Corcoran, Elise M Stewart, Dzung Do-Ha, Monique Bax, Gilles Guillemin, Kara L Vine, Danny M Hatters, Heath Ecroyd, Christopher M Dobson, Bradley J Turner, Lezanne Ooi, Mark R Wilson, Neil R Cashman, Justin J Yerbury

2015-10-31

BACKGROUND: Amyotrophic Lateral Sclerosis is characterized by a focal onset of symptoms followed by a progressive spread of pathol..

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Effect of thymic stimulation of CD4 T cell expansion on disease onset and progression in mutant SOD1 mice

Rebecca K Sheean, Richard H Weston, Nirma D Perera, Angela D'Amico, Stephen L Nutt, Bradley J Turner

2015-02-27

BACKGROUND: The peripheral immune system is implicated in modulating microglial activation, neurodegeneration and disease progress..

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The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size

KI Watt, BJ Turner, A Hagg, X Zhang, JR Davey, H Qian, C Beyer, CE Winbanks, KF Harvey, P Gregorevic

2015-01-01

The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ dev..

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Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice

Bradley J Turner, Neza Alfazema, Rebecca K Sheean, James N Sleigh, Kay E Davies, Malcolm K Horne, Kevin Talbot

2014-04-01

Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels ..

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Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms

Leslie I Grad, Justin J Yerbury, Bradley J Turner, William C Guest, Edward Pokrishevsky, Megan A O'Neill, Anat Yanai, Judith M Silverman, Rafaa Zeineddine, Lisa Corcoran, Janet R Kumita, Leila M Luheshi, Masoud Yousefi, Bradley M Coleman, Andrew F Hill, Steven S Plotkin, Ian R Mackenzie, Neil R Cashman

2014-03-04

Amyotrophic lateral sclerosis (ALS) is predominantly sporadic, but associated with heritable genetic mutations in 5-10% of cases, ..

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

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

2014-03-04

Bioenergetic abnormalities and metabolic dysfunctionoccur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models..

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The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Catherine E Winbanks, Justin L Chen, Hongwei Qian, Yingying Liu, Bianca C Bernardo, Claudia Beyer, Kevin I Watt, Rachel E Thomson, Timothy Connor, Bradley J Turner, Julie R McMullen, Lars Larsson, Sean L McGee, Craig A Harrison, Paul Gregorevic

2013-10-28

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting..

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Dysregulation of the complement cascade in the hSOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis

John D Lee, Nur A Kamaruzaman, Jenny NT Fung, Stephen M Taylor, Bradley J Turner, Julie D Atkin, Trent M Woodruff, Peter G Noakes

2013-09-26

BACKGROUND: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral scle..

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CO-REGULATION OF SURVIVAL OF MOTOR NEURON AND BCL-XL EXPRESSION: IMPLICATIONS FOR NEUROPROTECTION IN SPINAL MUSCULAR ATROPHY

RS Anderton, LL Price, BJ Turner, BP Meloni, C Mitrpant, FL Mastaglia, C Goh, SD Wilton, S Boulos

2012-09-18

Spinal muscular atrophy (SMA), a fatal genetic motor disorder of infants, is caused by diminished full-length survival of motor ne..