AHA1 inhibition reduces tau accumulation

In a paper published in Proceedings of the National Academy of Sciences, researchers at the University of South Florida and University of Kansas showed that inhibition of activator of heat shock protein 90 (Hsp90) ATPase activity 1 (AHA1) reduces tau accumulation, suggesting that inhibiting the protein could treat tauopathies, including Alzheimer's disease.

In human embryonic kidney cells, the combination of Hsp90 and AHA1 increased tau aggregation compared with Hsp90 alone. In the cells, the researchers showed a small molecule inhibitor of AHA1 inhibited the interaction between the proteins and decreased accumulation of insoluble tau and tau fibril formation compared with vehicle. In a mouse model of tauopathy, AHA1 overexpression increased oligomeric and insoluble tau and increased neuronal loss and memory deficits compared with normal AHA1 expression. Additionally, colocalization of AHA1 and tau tangles was higher in postmortem brain tissue from AD patients than from healthy age-matched controls...