Study Rationale:
Parkinson’s disease is caused by the death of dopaminergic neurons in the brain. We propose that the immune system plays a key role in the death of dopaminergic neurons during PD via a mechanism called autoimmunity, when the immune system starts to attack our own cells. The lysosome, a small organelle that is present in all cells, plays a key role in the initiation of autoimmune mechanisms. A protein in lysosomes, glucocerebrosidase (GCase), is directly associated with PD, as shown by the higher incidence of the disease in people with a mutation in the gene (GBA) that makes GCase. Interestingly, we observed that the level of GCase expression in immune cells influences their ability to engage autoimmune mechanisms.
Study Design:
In our research project, we will study the role of GCase in autoimmune mechanisms in a variety of immune cells, as well as in disease models where GBA is mutated.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Linking GCase and GBA mutations to lysosomal dysfunction and autoimmunity will allow us to target the immune system for the development of novel therapeutic approaches. This is particularly interesting considering the fact that autoimmune mechanisms are likely to be engaged very early in the disease, before the killing of dopaminergic neurons, suggesting that treatment could be applied to prevent the emergence of motor impairments.