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Phosphatase Activity Toward Abnormally Phosphorylated τ: Decrease in Alzheimer Disease Brain
Abstract
Abstract: Microtubule‐associated protein τ is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated τ can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase‐1, 2A, and 2B in vitro. In the present study, we have developed an assay to measure protein phosphatase activity toward τ‐1 sites (Ser 199/Ser 202) using the hyperphosphorylated τ isolated from Alzheimer disease brain as substrate. Using this assay, we have identified that in normal brain, protein phosphatase‐2A and 2B and, to a lesser extent, 1 are involved in the dephosphorylation of τ. The Km values of dephosphorylation of the hyperphosphorylated τ by protein phosphatase‐2A and 2B are similar. The τ phosphatase activity is decreased by ∼30% in brain of Alzheimer disease patients compared with those of age‐matched controls. These findings suggest that a defect of protein phosphatase could be the cause of the abnormal hyperphosphorylation of τ in Alzheimer disease.
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Citations
Cited by
Tau pathology in Alzheimer disease and other tauopathies
Iqbal, K., del C. Alonso, A., Chen, S., Chohan, M. O., El-Akkad, E., Gong, C.-X., Khatoon, S., Li, B., Liu, F., Rahman, A., et al. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.09.008 · Cited by 1,037
Alonso, A. D. C., Grundke-Iqbal, I., & Iqbal, K. (1996) · Nature Medicine · doi:10.1038/nm0796-783 · Cited by 859
Self-citationTau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806
Self-citationLiu, F., Grundke‐Iqbal, I., Iqbal, K., & Gong, C. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04391.x · Cited by 759
Self-citationMechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628
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Metadata
- Authors
- Gong, C., Shaikh, S., Wang, J., Zaidi, T., Grundke‐Iqbal, I., & Iqbal, K.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1995-08
- Volume
- 65
- Issue
- 2
- Pages
- 732-738
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2056470407
- Cited by
- 438
- References
- 0
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
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- Gong, C., Shaikh, S., Wang, J., Zaidi, T., Grundke‐Iqbal, I., & Iqbal, K. (1995). Phosphatase Activity Toward Abnormally Phosphorylated τ: Decrease in Alzheimer Disease Brain. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.1995.65020732.x
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