Dr Natura Myeku has a long-standing interest in understanding the mechanism of deficient protein quality control in tauopathy disorders that have a common feature—accumulation of pathological tau. In particular, she is interested in studying the ubiquitin proteasome system (UPS), which is the principal pathway for protein turnover in eukaryotic cells.
Her lab uses unique transgenic mouse models of 26S proteasome and tauopathy to identify mechanisms associated with dysregulated clearance of tau and disease progression. Another major focus of the lab’s research is translating our knowledge of the UPS biology into novel therapeutic approaches for treatment of Alzheimer’s disease and possibly other proteotoxic diseases.
Her lab has demonstrated that phosphorylation of 26S proteasomes, by clinically relevant drugs, can lead to activated proteasome proteolysis, resulting in decreased insoluble tau levels, attenuated tauopathy and rescued cognitive performance.
Current in vivo projects are underway to identify pathways for on-target, locally restricted proteasome activation in neurons where misfolded proteins accumulate first in early stages of Alzheimer’s disease.