Microtubule Stabilizing Agents as Potential Treatment for Alzheimer's Disease and Related Neurodegenerative Tauopathies

The microtubule (MT) associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation, and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeatic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds.