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Mouse study identifies protective mechanism against alcohol-induced embryo toxicity

Researchers have identified a mechanism by which the eight amino acid peptide NAP, an active fragment of a neuroprotective brain protein, protects against alcohol-induced embryo toxicity and growth retardation in mice. Their findings bring alcohol researchers a critical step closer to developing pharmacologic agents to prevent alcohol-induced fetal damage. The study, funded by the National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Child Health and Human Development (NICHD), and the Medical Research Service, Department of Veterans Affairs, appears in the current issue of the Proceedings of the National Academy of Sciences.*

The researchers produced NAP derivatives with specific substitutions and screened the compounds in cultured rat neurons for their protection against cell toxins and in whole mouse embryos for their protection against alcohol. By manipulating NAP's structure and thereby altering its activity, the researchers were able to examine the ability of the different NAP derivatives to block alcohol inhibition of the L1 cell adhesion molecule. Their results indicate that NAP protects mouse embryos from alcohol toxicity by blocking alcohol effects on L1 rather than by its broad neuroprotective actions.

"This elegant study demonstrates that the protective effect of NAP against alcohol damage differs from that of NAP against neurotoxins, said Ting-Kai Li, M.D., Director, National Institute on Alcohol Abuse and Alcoholism. "Ethanol inhibition of L1 is now strongly implicated in the pathogenesis of fetal alcohol damage and a foremost target of medication development."

Michael Charness, M.D., of the Veterans Administration Boston Healthcare System and Department of Neurology, Harvard Medical School, headed up the study, with colleagues from the NICHD and the University of North Carolina Bowles Center for Alcohol Studies.

NAP, technically known as NAPVSIPQ, is known t
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Contact: Ann Bradley
abradley@willco.niaaa.nih.gov
301-443-0595
NIH/National Institute on Alcohol Abuse and Alcoholism
9-Jun-2003


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