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Fig. 3. Tau phosphorylation plays both physiological and pathological roles in the cell. When the phosphorylation state of tau is appropriately coordinated, it plays a role in regulating neurite outgrowth (Biernat and Mandelkow, 1999; Biernat et al., 2002), axonal transport (Spittaels et al., 2000; Tatebayashi et al., 2004) and microtubule stability and dynamics (Cho and Johnson, 2004). However, in pathological conditions in which there is an imbalance in the phosphorylation/dephosphorylation of tau, aberrant tau phosphorylation can cause tau filament formation (Abraha et al., 2000), disrupt microtubule-based processes owing to decreased microtubule binding (Lu and Wood, 1993) and perhaps even increase cell death (Fath et al., 2002).
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