J Neurosci. 2007 Nov 21;27(47):12808-16.
Methionine sulfoxide reductase A and a dietary supplement S-methyl-L-cysteine prevent Parkinson's-like symptoms.

Wassef R, Haenold R, Hansel A, Brot N, Heinemann SH, Hoshi T.
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

...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.
PMID: 18032652 [PubMed - indexed for MEDLINE]

hello dear jaye!

I am no professor of chemistry -
all I do is try to find the childs version with pictures -of explanations
and read...


organic compound, one of the 20 amino acids commonly found in animal proteins. Only the L-stereoisomer participates in the biosynthesis of mammalian protein. It is particularly abundant in the proteins of hair, hooves, and the keratin of the skin. Cysteine's importance is related to the presence of a sulfur-containing thiol group in its side chain. This group participates in the catalytic reactions of certain enzymes, such as that of papain, the enzyme from papaya latex used to make commercial meat tenderizers. The thiol group of one cysteine residue is capable of combining with the thiol group of another to form a disulfide bridge, either linking two peptide chains together, as in the case of insulin, or causing a single peptide chain to fold back on itself, making a loop. This latter effect on the secondary structure of proteins is evidently of great importance in maintaining the proper configuration of both structural proteins and enzymes. Two cysteine molecules linked together by a disulfide linkage make up the amino acid cystine, often occurring as a separate entry in lists of common amino acids. A major complication of cystinuria, an inherited metabolic disease, one of whose symptoms is a twentyfold to thirtyfold increase in urinary excretion of cystine, is the precipitation of this relatively insoluble amino acid in the kidney, impairing its function. A similar sort of renal failure often accompanies cystinosis, another inherited disease. Cystine was isolated from a urinary calculus in 1810 and from horn tissue in 1899. The reduction of cystine to cysteine was reported in 1884, and the structures of the two amino acids were proved by chemical synthesis in 1903–4. Neither cysteine nor cystine is essential to the diet of man; cystine and cysteine are interconvertible, and cysteine is made in the body from serine and methionine.

more info - at

http://www.answers.com/l-cysteine?ca...&ver=2.3.0.609

in proteins that is most easily modified by oxidation. In its normal, reduced form, it has so-called non-polar or hydophobic properties. That is, it has little tendency to interact with water, a typical polar substance. The side-chain of methionine, a -CH2-S-CH3 group, is readily oxidised to the corresponding sulfoxide, -CH2-CO-CH3, which has polar properties. In that form it is very comfortable interacting with water, and less likely to interact with non-polar, "oily" environments present in a protein where it resides. The polar-vesus-nonpolar interactions are important for maintaining proper, "native" structure in proteins, so keeping methionine in its recduced, non-polar state is likely to be important for retaining the normal shape and function of the proteins in which it exists.

So, think about the normal structure of a protein as having its parts with polar amino acids on the "outside", in contact with water, whereas the parts with nonpolar amino acids down inside the middle of the structure, forming its "oily", nonpolar center.

This research involved producing transgenic drosophila (fruit flies) which had a human alpha synuclein gene added to its genome. Alpha synuclein is one of the proteins for which abnormalities in its structure or behavior (it is a major component of Lewey bodies found in PD brains) is associated with Parkinsons.
I gather that the "ectopic" (abnormal location) production of the human alpha synuclein in these insects was caused by or associated with oxidation of methionine in that or some other protein. The S-methyl cyseine compound found in garlic and cabbage apparently enhances the activity of methionine sulfoxide reductase, an enzyme that catalyzes conversion back to the "normal" reduced amino acid, presumably correcting the disrupted protein structure and preventing abnormal behavior in the flies related to the ectopically produced human alpha synuclein.

One interpretation of this result would be "Putting human alpha synuclein in fruit flies, in addition to their own alpha synuclein, gums up its nervous system in a process that involves oxidation of methionine." How this process is related to PD is not clear to me.

Robert