Pathogenic tau aggregation is one of the major hallmarks associated with Alzheimer’s disease and a number of other tauopathies. The microtubule‑associated protein tau forms neurotoxic aggregates that promote cognitive deficits in tauopathies. The 90 kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood‑brain barrier permeable and many present associated toxicities.
Our inventors have discovered a treatment for the effective inhibition of the Hsp90 cofactor Aha-1 via a small molecule inhibitor. This treatment has the potential to significantly reduce tau levels and may ultimately reduce neuronal loss and cognitive decline that is associated with Aha-1 over-expression. This method of inhibiting the HSP90 system and its co-factors presents a valuable target for the treatment of Alzheimer’s disease and other tauopathies.
Image Displays HSP90 and its Co-Factors Enhancing Tau Fibril Formation