Kinase inhibitors were some of the first drugs to be tested to treat tauopathies for several reasons. Even though phosphorylation has not been proven to play a role in toxicity, hyperphosphorylated tau was originally seen as an attractive target because it is an early marker of the disease that precedes aggregation in AD. Kinase inhibition was accessible, as enzymes are traditional druggable targets and kinase inhibitors had been developed for many years for the treatment of cancer and psychiatric disorders. However, kinase inhibitors have also been historically difficult to develop outside of the oncology field because they are often unspecific and similar related kinases are also inhibited. Kinases also have many roles and numerous substrates, so even in the event that an inhibitor is specific, the unintended off-target effects may still represent an important liability.
