Neurodegeneration Seminar // Mechanistic link between LRRK2, alpha-synuclein, and lysosomal function

Recent advances in the genetics and developmental biology of Parkinson’s Disease (PD) have greatly expanded our understanding of this common neurodegenerative disorder and have begun to identify desperately needed new approaches to therapy. In this talk I will discuss the potential direct role of the mutated gene encoding leucine-rich repeat kinase 2 (LRRK2) in dysregulating lysosomal pathways and in causing a pathologically synergistic interaction between LRRK2 and PD risk factors such as the aberrant expression of alpha-synuclein. Our data support a role for impaired autophagy in PD with cross-talk between macroautophagy and chaperone-mediated autophagy. These findings may help to clarify how interactions between LRRK2, alpha-synuclein, and autophagy processes contribute to the pathogenesis of Parkinson’s Disease.