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...

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Bibliographic Details
Published in:Trends in molecular medicine 2009-03, Vol.15 (3), p.112-119
Main Authors: Hanger, Diane P, Anderton, Brian H, Noble, Wendy
Format: Article
Language:English
Subjects:
Animals
Humans
Pathology
Phosphorylation
Phosphotransferases - analysis
Phosphotransferases - metabolism
tau Proteins - analysis
tau Proteins - chemistry
tau Proteins - metabolism
Tauopathies - drug therapy
Tauopathies - physiopathology
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Summary: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.
ISSN:1471-4914
1471-499X
DOI:10.1016/j.molmed.2009.01.003