Tau phosphorylation: the therapeutic challenge for neurodegenerative disease.
The microtubule-associated protein tau is integral to the pathogenesis of Alzheimer's disease (AD), as well as several related disorders, termed tauopathies, in which tau is deposited in affected brain regions. In the tauopathies, pathological tau is in an elevated state of phosphorylation and is aberrantly cleaved. It also exhibits abnormal conformations and becomes aggregated, resulting in neurofibrillary tau pathology. Recent evidence suggests that relatively early disease-associated changes in soluble tau proteins, including phosphorylation, are involved in the induction of neuronal death. Here, we summarize recent developments that suggest new therapeutic strategies to prevent or reduce the progression of pathology in the tauopathies. A list of tau phosphorylation sites identified in the tauopathies and in controls accompanies this review.
Hanger
Diane P
DP
MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. Diane.Hanger@kcl.ac.uk
Anderton
Brian H
BH
Noble
Wendy
W
D000818:Animals; D006801:Humans; D010766:Phosphorylation; D010770:Phosphotransferases / Q000032:analysis / Q000378:metabolism; D024801:Tauopathies / Q000188:drug therapy* / Q000503:physiopathology*; D016875:tau Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
D016875:tau Proteins; D010770:Phosphotransferases