Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 33, Issue -, Pages S123-S139Publisher
IOS PRESS
DOI: 10.3233/JAD-2012-129031
Keywords
Alzheimer's disease; neurofibrillary degeneration; post-translational modifications of tau; protein kinases; protein phosphatases; tau phosphorylation
Categories
Funding
- New York State Office of People
- Developmental Disabilities
- NIH [TW008744-01A1, AG019158, AG028538]
- FOGARTY INTERNATIONAL CENTER [R03TW008744] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG028538, R01AG019158] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Microtubule associated protein tau is a phosphoprotein which potentially has 80 serine/threonine and 5 tyrosine phosphorylation sites. Normal brain tau contains 2-3 moles of phosphate per mole of the protein. In Alzheimer's disease brain, tau is abnormally hyperphosphorylated to a stoichiometry of at least three-fold greater than normal tau, and in this altered state it is aggregated into paired helical filaments forming neurofibrillary tangles, a histopathological hallmark of the disease. The abnormal hypelphosphorylation of tau is also a hallmark of several other related neurodegenerative disorders, called tauopathies. The density of neurofibrillary tangles in the neocortex correlates with dementia and, hence, is a rational therapeutic target and an area of increasing research interest. Development of rational tau-based therapeutic drugs requires understanding of the role of various phosphorylation sites, protein kinases and phosphatases, and post-translational modifications that regulate the phosphorylation of this protein at various sites, as well as the molecular mechanism by which the abnormally hyperphosphorylated tau leads to neurodegeneration and dementia. In this article we briefly review the progress made in these areas of research.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available