Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis

Brain : a Journal of Neurology
Kevin X LiuPeter L Oliver

Abstract

Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A)...Continue Reading

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Citations

Apr 3, 2016·Free Radical Biology & Medicine·Yixing WuPeter L Oliver
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Methods Mentioned

BETA
transgenic
immunoprecipitation
PCR
biopsies

Software Mentioned

Ingenuity
AxioVision
ImageJ
GraphPad
Ingenuity Pathways Analysis tool
GeneSpring
limma
Prism

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