Urate mitigates oxidative stress and motor neuron toxicity of astrocytes derived from ALS-linked SOD1G93A mutant mice

Publication date: October 2018Source: Molecular and Cellular Neuroscience, Volume 92Author(s): Rachit Bakshi, Yuehang Xu, Kaly A. Mueller, Xiqun Chen, Eric Granucci, Sabrina Paganoni, Ghazaleh Sadri-Vakili, Michael A. SchwarzschildAbstractDominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease characterized by loss of motor neurons. Oxidative stress has also been linked to many of the neurodegenerative diseases and is likely a central mechanism of motor neuron death in ALS. Astrocytes derived from mutant SOD1G93A mouse models or patients play a significant role in the degeneration of spinal motor neurons in ALS through a non-cell-autonomous process. Here we characterize the neuroprotective effects and mechanisms of urate (a.k.a. uric acid), a major endogenous antioxidant and a biomarker of favorable ALS progression rates, in a cellular model of ALS. Our results demonstrate a significant protective effect of urate against motor neuron injury evoked by mutant astrocytes derived from SOD1G93A mice or hydrogen peroxide induced oxidative stress. Overall, these results implicate astrocyte dependent protective effect of urate in a cellular model of ALS. These findings together with our biomarker data may advance novel targets for treating motor neuron disease.
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research