Patients with Parkinson's disease suffer from a lack of dopamine. This deficiency causes the hyperactivity of certain neurons that are responsible for the control of movement. The neurons of the subthalamic nucleus are overexcited and contribute to sending erroneous information to the motor cortex. This in turn leads to the appearance of debilitating symptoms such as muscular rigidity, paralysis, etc. "Yet we are not sure of precisely all the events that occur in between the lack of dopamine and the symptoms," says Erwan Bezard of the "Physiologie et physiopathologie de la signalisation cellulaire" Laboratory (CNRS - University of Bordeaux 2). Along with other CNRS scientists and colleagues at the University of Manchester and the University Hospital of Toronto, this researcher unveiled one of these intermediary steps. The scientists worked on a peptide called Sonic Hedgehog. They identified its function and discovered that Sonic Hedgehog participates in the control of the activity of the subthalamic nucleus.
Before the researchers took an interest in this protein, its role in the adult brain was not understood. They, however, observed that its expression is reduced in an experimental model of Parkinson's disease, i.e., when patients suffer a dopamine deficiency. The scientists wondered if Sonic Hedgehog might play a role in the disease. They then showed that the protein inhibits the activity of the subthalamic neurons and proved this by conducting experiments on rats: the activity of the subthalamic nucleus was reduced when the protein was applied directly to it.
Now the researchers would like to show that "increasing the Sonic Hedgehog signal in the subthalamic region may offer a potential treatment for Parkinson's disease." Before they can consider clinical applications, they must ascertain that the protein plays the same role in the brain of primates. Although the researchers have shown that the expression of Sonic Hedgehog is comparable, behavioral experiments have not yet been carried out in primates. If such experiments provide encouraging results, it may be possible to envisage new, non-dopaminergic treatments for Parkinson's disease, which would probably cause fewer side effects than the dopaminergic treatments currently in use.