Targeting a protein might allow treatment of alcoholism and simultaneously prevent alcohol-induced heart and liver damage, researchers, including one of Indian-origin, have found.
The protein called RGS6 (regulator of G protein signalling 6) acts through two separate mechanisms to control alcohol-seeking behaviour and alcohol-induced cell death in heart, liver, and other organs.
“Given the prevalence of alcohol abuse worldwide there is a clear need for more effective therapeutics,” lead researcher Rory Fisher from the University of Iowa said.
“We propose that inhibiting this RGS6 protein could represent a new approach to counteract alcohol dependence and at the same time protect against the cell-killing actions of alcohol in the heart and liver,” said Fisher.
Previous work from Fisher’s lab had suggested that RGS6 might be important in signalling pathways in the brain that appear to be involved in addiction and alcohol dependence.
The team, including first author Adele Stewart and Biswanath Maity, used mice lacking RGS6 to probe the protein’s roles in both alcohol craving and organ damage.
The researchers found that mice without the RGS6 protein consumed less alcohol than wild-type mice when given free access.
The mice without RGS6 also were less susceptible to alcohol-induced reward and had less severe and shorter-lived alcohol withdrawal symptoms.
At the same time, when mice that lacked the RGS6 protein were treated chronically with alcohol, they experienced less damage to heart and liver as well as the lining of the gut compared to mice with the protein.
“To our knowledge RGS6 is the only gene with a demonstrated ability to promote alcohol-seeking behaviours while simultaneously worsening the damaging effects of alcohol consumption on the heart, stomach, intestine and liver,” Fisher said.
The study showed although the same protein is involved in these two different effects, the biological mechanisms that produce the effects are different.
In the brain, RSG6 is involved in alcohol craving by controlling levels of dopamine, a neurotransmitter associated with addiction and reward-seeking behaviour.
In the heart and liver, RSG6’s effect is based on its role in a pathway that causes cell death through production of damaging compounds called reactive oxygen species.
There currently are only a few drugs that purport to treat alcohol dependence and none that treat the damaging effects alcohol has on various organs.
The study suggests that targeting the actions of RGS6 might accomplish both aims.
The study was published in the journal PNAS.