Small molecule research, which can protect dopaminergic neurons (or dopamine producers) from the numerous events involved in cell death remains an intensive research focus. However, few compounds have shown an effect, both on in vitro neuronal cultures, and in animal models of Parkinson’s disease in vivo.
Researchers from the ICM and the Lab “Biomolecules : conception, isolation and synthesis” have used natural substances and have changed their structure. These natural substances, present in very small quantity in tropical plants of the Annonaceae family, had not however a good pharmacological profile, and were particularly inefficient to go through the blood-brain barrier.
After having synthesized a new compound library and observed their biological activity, they succeeded in characterising a new fully synthetic molecule, the 3-phenyl-6-aminoquinoxaline (PAQ), which perfectly targets neuronal cells. By activating specific receptors, the PAQ manages to restore intracellular calcium balance, one of the mechanisms invoked to explain the neuro-protective effect.
Researchers have highlighted this effect during in vitro studies, in rat dopaminergic neuron primary cultures. Then, in an animal model of Parkinson’s disease, they have shown that dopamine concentrations were partially restored to provide nerve impulse.
This work will possibly open the way, ultimately, for a curative treatment for Parkinson’s disease.