The researchers have called the gene "hangover", and believe that a similar version may exist in humans which could explain why alcoholism seems to run in families.

The study found that the gene helps fruit flies to develop a tolerance to alcohol, a condition which in humans leads to dependency and addiction.

According to Ulrike Heberlein of the University of California in San Francisco, flies lacking the hangover gene do not develop the tolerance seen in those with the gene.

Dr Heberlein says that repeated alcohol consumption leads to the development of tolerance, which is simply defined as an acquired resistance to the physiological and behavioural effects of the drug.

It is this tolerance, she says that allows increased alcohol consumption, that eventually leads to physical dependence and addiction.

The scientists say that in nature, fruit flies are often exposed to alcohol in rotting fruit, and there is strong evidence to suggest that the drug has a similar effect on the insects.

Heberlein says that when flies are exposed to ethanol vapour, they become hyperactive, uncoordinated and eventually sedated.

In another discovery the research team found that, as well as making the flies more tolerant of alcohol, the hangover gene appeared to influence the way the insects responded to stressful conditions in their environment, such as increased temperature.

The scientists suspect that the gene may perhaps play a more general role in dealing with stressful conditions, and its influence on alcohol tolerance, is merely a side-effect.

It is therefore possible, say the scientists, that this might also happen in humans, suggesting that addiction may initially be triggered by the way in which the body responds to stressful factors, such as high alcohol intake.

The study is published in the journal Nature.

Nature and ucsf/

As a result of several additional experiments done in his lab and by other groups, Dr. Hayward suspected that the mutant proteins might be more vulnerable than the normal enzyme to specific stresses in tissues. In their Journal of Biological Chemistry paper, Dr. Hayward and his colleagues at the University of Massachusetts Medical School show that when the mutant SOD1 enzymes are exposed to reagents that can disrupt some of the protein's bonds or remove its metal ions, they become much stickier than the normal protein.

"The mutants, but not the normal SOD1, adhere to a hydrophobic or 'greasy' surface, and this property could promote abnormal interactions with other proteins or membranes in the cell," explains Dr. Hayward. "How well different tissues can handle this burden of sticky protein, especially during aging, may be one factor that determines which cell types are most vulnerable in the disease. It was interesting to us that the adherent forms were not restricted to the nervous system in the mouse models but were also seen in other tissues such as heart and skeletal muscle. It is possible that this property could contribute to abnormalities in muscle, while other tissues such as kidney do not accumulate hydrophobic SOD1 despite a high expression level of the mutants."

These results may lead to new treatments for some forms of ALS. For example, if researchers can minimize the hydrophobic exposure or can understand how certain tissues prevent build-up of the sticky forms of SOD1, they might be able to boost defenses in tissues known to be susceptible to mutant SOD1 accumulation.

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