Neurodegenerative and Lysosomal Storage Diseases: iPS Cell-Based Disease Models to Study the Role of Autophagy

Autophagy, a major protein degradation pathway, has been implicated in a myriad of human physiological and pathological conditions like development, immunity, longevity, cancer, myopathies, liver diseases and neurodegeneration. Impaired autophagy has been suggested to be a major contributing factor in a variety of neurodegenerative diseases, which are associated with progressive cognitive decline and degeneration in the brain. This research project focuses on the patients with Parkinson’s disease (PD) and Niemann-Pick disease type C1 (NPC1). Both the diseases are associated with severe neurodegeneration, along with liver dysfunction in NPC1, which is also a lysosomal storage disorder.

To examine whether dysfunctional autophagy can directly contribute to neurodegeneration, genetic tools will be employed to introduce mutations that affect autophagy pathways in wild-type and disease-specific cells. The long-term goal of this project is to assess the causal relation between impaired autophagy and development of neurodegeneration, and to set up systems to screen for drugs that could serve as therapeutic targets.