Progressive Multiple Sclerosis (PMS) is characterized by the continued and irreversible accumulation of neurodegeneration and consequently, neurologic disability. No therapy is available to arrest neurodegeneration and disease progression in PMS and other neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease. This lack of disease modifying therapies reflects a conceptual deficit in our understanding of the underlying pathology that drives neurodegeneration. Recent findings suggest that innate immune cells in the central nervous system (CNS) - astrocytes, microglia and infiltrating macrophages - play a predominant role in promoting neurodegeneration in PMS and other neurodegenerative disorders such as Alzheimer's and Parkinson's Disease. However, the mechanisms that control CNS innate immunity and neurodegeneration are not known.
The long-term goal of this project is to develop new therapies to arrest neurodegeneration. Our central hypothesis is that the innate immune response in the CNS drives neurodegeneration and provides unique therapeutic approaches for other neurodegenerative diseases. In particular, we will: 1) Establish a zebrafish model to study molecular mechanisms of neurodegeneration; 2) Generate shRNA- and CRISPR-based tools to study candidate genes in in-vitro and in-vivo mammalian models; 3) Investigate the effect of candidate genes using in-vivo and in-vitro models of neurodegeneration.