EP300 and neurodegenerative disease: To delineate the direct effect of tau acetylation on clinical tauopathy in human neurodegenerative diseases, we prepared a series of tau mutants, in which individual lysine residues were replaced by alanine (tauK174A, tauK274A, tauK280A, and tauK231A), and expressed them in SH-SY5Y cells with p300 (Figure 1, F and G).