Cellular surveillance system identifies misfolded proteins and tags them for proteasomal degradation. Accumulation of misfolded and aggregated proteins compromises the ubiquitin-proteasome system and may underlie the age-dependent decline of proteasome activity, which progressively leads to neurodegenerative diseases. Activation of the proteasome activity using genetic and pharmacological approaches has been shown to ameliorate neurodegenerative phenotypes in several animal models of neurodegeneration.
Using biochemical and genetic screening, we identified novel regulators of the protein degradation system that can effectively accelerate cellular protein breakdown. We aim to understand their biological mechanisms and how their regulation may be involved in neurodegeneration. We hope our study will lead to novel therapeutic approaches to target neurodegenerative diseases.