The ability to selectively destroy harmful proteins could represent a powerful therapeutic approach in several diseases. Our work focusses on a newly discovered arm of immunity that operates in the intracellular environment. Viruses that import antibody to the cell during infection are detected by a dedicated intracellular antibody receptor, TRIM21. We have demonstrated that cytosolic host-derived proteins can be similarly targeted for selective degradation in this manner. Seeded aggregation of tau, a process thought to occur in Alzheimer's diseases and other neurodegenerative disorders, can be inhibited by antibody/TRIM21. Our Cytosolic Protein Targeting group seeks to understand the molecular details of how challenging substrates such as assemblies of tau can be processed by cellular machinery. We ask whether cytosolic protein targeting is a relevant and plausible method for selectively targeting pathological proteins during neurodegeneration.
