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The Journal of Neuroscience, November 21, 2007, 27(47):12808-12816; doi:10.1523/JNEUROSCI.0322-07.2007

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Neurobiology of Disease
Methionine Sulfoxide Reductase A and a Dietary Supplement S-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Ramez Wassef,¹ Ronny Haenold,¹ Alfred Hansel,² Nathan Brot,³ Stefan H. Heinemann,² and Toshinori Hoshi¹

¹Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, ²Centre for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena, D-07747 Jena, Germany, and ³Hospital for Special Surgery, Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021

Correspondence should be addressed to Dr. Toshinori Hoshi, Department of Physiology, University of Pennsylvania, Richards D100, 3700 Hamilton Walk, Philadelphia, PA 19104. Email: hoshi{at}hoshi.org

Parkinson's disease (PD), a common neurodegenerative disease, is caused by loss of dopaminergic neurons in the substantia nigra. Although the underlying cause of the neuronal loss is unknown, oxidative stress is thought to play a major role in the pathogenesis of PD. The amino acid methionine is readily oxidized to methionine sulfoxide, and its reduction is catalyzed by a family of enzymes called methionine sulfoxide reductases (MSRs). The reversible oxidation-reduction cycle of methionine involving MSRs has been postulated to act as a catalytic antioxidant system protecting cells from oxidative damage. Here, we show that one member of the MSR family, MSRA, inhibits development of the locomotor and circadian rhythm defects caused by ectopic expression of human -synuclein in the Drosophila nervous system. Furthermore, we demonstrate that one way to enhance the MSRA antioxidant system is dietary supplementation with S-methyl-L-cysteine (SMLC), found abundantly in garlic, cabbage, and turnips. SMLC, a substrate in the catalytic antioxidant system mediated by MSRA, prevents the -synuclein-induced abnormalities. Therefore, interventions focusing on the enzymatic reduction of oxidized methionine catalyzed by MSRA represent a new prevention and therapeutic approach for PD and potentially for other neurodegenerative diseases involving oxidative stress.

Key words: oxidative stress; Parkinson's disease; methionine; methionine sulfoxide reductase; dietary supplement; synuclein

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Received Jan. 24, 2007; revised Sept. 26, 2007; accepted Sept. 28, 2007.

Correspondence should be addressed to Dr. Toshinori Hoshi, Department of Physiology, University of Pennsylvania, Richards D100, 3700 Hamilton Walk, Philadelphia, PA 19104. Email: hoshi{at}hoshi.org

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