Age-dependent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, share common characteristics of late age onset, the presence of protein aggregates in the brain, and neurodegeneration. Protein misfolding and aggregation is intimately related to disease progress. Our research aims to understand how protein misfolding occurs during disease and how misfolded protein aggregates cause neurodegeneration. Our overall goal is to develop effective prophylactic and therapeutic approaches to prevent and reverse protein aggregation and neurodegeneration.
Transmissible spongiform encephalopathies (TSEs; also known as prion diseases) are a unique set of this group of disorders. Besides the sporadic and inherited forms, TSEs are also bona fide infectious diseases, examples of which include Creutzfeldt–Jakob disease in humans, scrapie in sheep, and chronic wasting disease in deer and elk. The infectious agent of TSEs is called a prion, a misfolded isoform of a normal host-encoded protein. Using the recombinant prion technique established in our lab, we are unraveling the molecular characteristics of a prion, which will allow us to develop strategies to detect and neutralize this unorthodox infectious agent.
Recent advances in the field of neurodegenerative diseases reveal that other misfolded protein aggregates, such as alpha-synuclein in Parkinson’s disease, spread the disease pathology in a “prion-like” manner; that is, misfolded protein aggregates are able to spread from a sick cell to a healthy cell and seed protein aggregation. We are interested in understanding what misfolded protein aggregates are responsible for such a prion-like spread of pathology, how much they contribute to the pathogenic changes, and how they can be modulated.