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WWOX limits Tau hyperphosphorylation and aggregation. The C-terminal SDR domain of WWOX physically binds GSK3β preventing hyperphosphorylation of Tau (Sze et al., 2004; Wang et al., 2012). Also, the first WW domain binds JNK, thereby preventing Tau hyperphosphorylation (Sze et al., 2004). The first WW domain binds ERK (Huang et al., 2016). Tau protein supports polymerization of tubulin monomers to assemble microtubules, which are needed for neurite outgrowth (Wang et al., 2012).
