The Molecular and Cellular Basis of Parkinson’s Disease 

Parkinson’s disease (PD) affects >1% of the population over the age of 65. Currently, there are over 100,000 people affected in Canada alone and the numbers will only grow as the population ages. PD involves the death of dopamine (DA) neurons in the midbrain, which leads to devastating motor and functional impairment. Moreover, it is becoming clear that PD pathology is not limited to DA neurons but is much more widespread, involving cells both inside and outside the brain. These non-DA lesions often precede DA involvement and help explain the many early non-motor symptoms in PD patients, which until recently have been largely ignored. Although treatment for PD is available, its effectiveness diminishes over the long term. Hope for a more definitive treatment lies in basic biomedical research. Over the past few years, the discovery of genes responsible for familial forms of PD, have transformed what had been considered until the late 1990s as a prototypic “environmental disease” into one of the most complex multi-genetic diseases of the brain. 

Our lab has had a longstanding interest in understanding the molecular and cellular functions of these PD genes. Mutations in the genes encoding α-synuclein, leucine-rich repeat kinase 2 (LRRK2) and Vps35 cause autosomal dominant forms of PD, whereas mutations in the genes encoding parkin, PINK1, and DJ-1 cause autosomal recessive forms of PD. Although these monogenic forms only account for ~5-10% of all PD cases, characterizing the molecular and cell biological mechanisms involved has become one of the most promising strategies for understanding the pathogenesis of the more common sporadic forms of PD. Below are some ongoing projects in the lab.  



2) Regulation of Parkin by Deubiquitination Read more

3) The Structural Basis of Parkin-Mediated Ubiquitination Read more 

4) Mechanism of cell-to-cell propagation of α-Synuclein Pathology in PD Read more

5) Function of other PD Genes  Read more