Methionine sulfoxide reductase A and a dietary supplement S-methyl-L-cysteine prevent Parkinson's-like symptoms.
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 alpha-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 alpha-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.
Wassef
Ramez
R
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Haenold
Ronny
R
Hansel
Alfred
A
Brot
Nathan
N
Heinemann
Stefan H
SH
Hoshi
Toshinori
T
D000818:Animals; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019587:Dietary Supplements; D004330:Drosophila; D006801:Humans; D051150:Methionine Sulfoxide Reductases; D009043:Motor Activity / Q000502:physiology; D010088:Oxidoreductases / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
C008425:S-methylcysteine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D003545:Cysteine