Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. Six isoforms with different amino-terminal inserts and different numbers of tandem repeats near the carboxy-terminus have been identified, and tau is hyperphosphorylated at approximately 25 sites by ERK, GSK-3 and CDK5 (1-2). Phosphorylation decreases the ability of tau to bind to microtubules. Neurofibrillary tangles are a major hallmark of Alzheimers disease and these tangles are bundles of paired helical filaments composed of hyperphosphorylated tau. In particular, phosphorylation of Ser396 by GSK-3 or CDK5 destabilizes microtubules in Alzheimers disease. Furthermore, inclusions of tau are found in a number of other neurodegenerative diseases, collectively known as tauopathies (1,3). Timm T, et al. (2003) EMBO J, 22(19): 5090-5101.
