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DJ-1 Changes in G93A-SOD1 Transgenic Mice: Implications for Oxidative Stress in ALS

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Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, neurodegenerative disorder. The causes of ALS are still obscure. Accumulating evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. DJ-1 plays an important role in the oxidative stress response. The aim of this study was to discover whether there are changes in DJ-1 expression or in DJ-1-oxidized isoforms in an animal model of ALS. We used mutant SOD1G93A transgenic mice, a commonly used animal model for ALS. Upregulation of DJ-1 mRNA and protein levels were identified in the brains and spinal cords of SOD1G93A transgenic mice as compared to wild-type controls, evident from an early disease stage. Furthermore, an increase in DJ-1 acidic isoforms was detected, implying that there are more oxidized forms of DJ-1 in the CNS of SOD1G93A mice. This is the first report of possible involvement of DJ-1 in ALS. Since DJ-1 has a protective role against oxidative stress, it may suggest a possible therapeutic target in ALS.

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  1. Laboratory of Neurosciences, Felsenstein Medical Research Center and Department of Neurology, Rabin Medical Center-Beilinson Campus, The Sackler School of Medicine, Tel Aviv University, Petah Tikva, 49100, Israel

    Nirit Lev, Debby Ickowicz, Yael Barhum, Eldad Melamed & Daniel Offen

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  1. Nirit Lev
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  2. Debby Ickowicz
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Lev, N., Ickowicz, D., Barhum, Y. et al. DJ-1 Changes in G93A-SOD1 Transgenic Mice: Implications for Oxidative Stress in ALS. J Mol Neurosci 38, 94–102 (2009). https://doi.org/10.1007/s12031-008-9138-7

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