The scientists made the surprising observation that SMN will bind efficiently -- and carry out its functions -- if the proteins to which it needs to bind are first "tagged" by specific enzymes. The tags are made up of methyl groups that are attached through the amino acid arginine to specific sites on SMN's protein targets (the process is 'methylation'), where they sit like "bumps" or "buttons" on the proteins' surface. In addition to unraveling the function of the methylation of arginines in proteins -- a common modification process that was first reported more than 30 years ago whose function remained unknown until now -- the findings may have important implications for neurodegenerative disease.
The methyl group tags are supplied by a "methyl donor" called SAM (for S-adensylmethionine), and SAM receives this methyl group from folic acid (also known as folate) through a pathway that requires vitamin B12.
This, the Penn researchers believe, raises the possibility that deficiency in folate (many vegetables, grains and fruits are especially rich in folate) or the B vitamins could be particularly detrimental to SMA patients -- because it could result in under-methylated proteins, which are exactly the kind of proteins SMN needs to find to function properly.
Since SMA patients are already compromised in their levels of SMN, they might be expected to be more severely afflicted by such nutritional deficiencies.
"We would like to say, very cautiously, that our work raises the possibility
that folic acid, and vitamin B12 may be helpful in lessening, even if only
slightly, the severity of the disease for some SMA patients-or at least
ensure that their condit
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Contact: Ellen O'Brien
ellen.obrien@uphs.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
24-May-2001