Parkinson’s Disease: Cracking the Molecular Code
Parkinson’s is a devastating degenerative disease characterized by severe movement disorders, such as shaking, stiffness and posture instability. Although it affects one in 300 people in industrialized countries and represents a heavy societal and economic burden, there is still no cure.
For a long time, Parkinson’s disease (PD) was thought to be caused by unknown environmental factors. But advances in genetics have revealed a number of genes that are implicated in familial PD. These genes are essentially recipes that neurons use to make proteins, which in turn protect these neurons from damage that accumulates over the years. Two proteins in particular—called Parkin and PINK1—have been shown to influence the quality control of mitochondria, the energy-producing organelle of the cell.
Research conducted by Dr. Jean-François Trempe, Canada Research Chair in Structural Pharmacology, has revealed how Parkin and PINK1 work. Using methods like X-ray crystallography, nuclear magnetic resonance and mass spectrometry, he and his research team have determined how PINK1 senses damage to mitochondria, and how this leads to the activation of Parkin, which cleans up the damage. Unfortunately, these proteins are defective in people with PD. But using structural analysis, Trempe and his team can now design prototype drugs that enhance their function.
This research program will improve our understanding of PD and could potentially lead to the development of new therapies to treat the more than 100,000 patients in Canada who suffer from Parkinson’s—a number that will only swell as the population ages.