MAPT and Alzheimer disease: In physiological conditions, the ubiquitin-proteasome system controls intracellular protein quality and eliminates misfolded and damaged proteins, however its activity in AD is impaired by oxidative stress, Aβ, tau, and aggregated and cross-linked cytosolic proteins that act as proteasome inhibitors, leading to the accumulation of toxic misfolded proteins and neuronal death [38–40].