A BRAIN protein newly linked to the waxing and waning of depression could be a key to treating this debilitating illness.
Depression is thought to be caused by some kind of breakdown in signalling by the brain chemical serotonin, and many antidepressants work by increasing the amount of serotonin available to cells. Now Paul Greengard of Rockefeller University in New York and his colleagues have found that a brain protein called p11 appears to make brain cells more receptive to serotonin. As levels of p11 rise, depression lifts in people and also in mice bred to be susceptible to depression.
The p11 protein appears to interact with the serotonin 1B receptor, which has been heavily implicated in depression. Both are formed inside brain cells, but when they interact 鈥減11 moves the 1B receptor to the membrane to make it functional鈥�, Greengard says. Autopsies of human brains have shown that concentrations of the protein are lowest in people who had been depressed immediately before they died. Mice genetically predisposed to depression also had low concentrations of the protein (Science, vol 311, p 77).
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Further experiments in mice genetically engineered to make either no p11 or too much showed that those without the p11 gene were depressed, while those with too much p11 were hyperactive.
鈥淭hose without the protein were depressed, while those with too much were hyperactive鈥�
By somehow boosting p11 levels, it might be possible to create an whole new generation of antidepressants. But it won鈥檛 be easy, Greengard warns. 鈥淵ou can鈥檛 give the protein to patients because it wouldn鈥檛 get into the brain. And even if it did, it wouldn鈥檛 get into cells.鈥�
So the race is on to find other ways of raising p11 levels, perhaps by identifying other genes and signalling molecules that control it. 鈥淲orking out the control of p11 and how to influence it seems a key objective,鈥� says psychiatrist Philip Cowen at the University of Oxford.
