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Developmental regulation of tau phosphorylation, tau kinases, and tau phosphatases
Abstract
Tau is a neuronal microtubule‐associated protein. Its hyperphosphorylation plays a critical role in Alzheimer disease (AD). Expression and phosphorylation of tau are regulated developmentally, but its dynamic regulation and the responsible kinases or phosphatases remain elusive. Here, we studied the developmental regulation of tau in rats during development from embryonic day 15 through the age of 24 months. We found that tau expression increased sharply during the embryonic stage and then became relatively stable, whereas tau phosphorylation was much higher in developing brain than in mature brain. However, the extent of tau phosphorylation at seven of the 14 sites studied was much less in developing brain than in AD brain. Tau phosphorylation during development matched the period of active neurite outgrowth in general. Tau phosphorylation at various sites had different topographic distributions. Several tau kinases appeared to regulate tau phosphorylation collectively at overlapping sites, and the decrease of overall tau phosphorylation in adult brain might be due to the higher levels of tau phosphatases in mature brain. These studies provide new insight into the developmental regulation of site‐specific tau phosphorylation and identify the likely sites required for the abnormal hyperphosphorylation of tau in AD.
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“Tau phosphorylation was shown to temporarily increase during development in rats during the period of active neurite outgrowth46.”
From Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation (2026) · cites this paper as [46]
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“Since the seminal discovery that abnormally hyperphosphorylated tau constitutes paired helical filaments (PHF) of neurofibrillary tangles (NFTs) (Grundke-Iqbal et al. 1986a; GrundkeIqbal et al. 1986b; Lee et al. 1991; Montejo de Garcini et al. 1986; Ihara et al. 1986), a hallmark brain lesion of Alzheimer disease (AD)…”
BackgroundPhosphorylation affects the ability of tau protein to promote microtubule assembly.
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The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease
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Metadata
- Authors
- Yu, Y., Run, X., Liang, Z., Li, Y., Liu, F., Liu, Y., Iqbal, K., Grundke‐Iqbal, I., & Gong, C.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-02-23
- Volume
- 108
- Issue
- 6
- Pages
- 1480-1494
- ISSN
- 0022-3042
- 1471-4159
- PMC
- PMC2676439
- Cited by
- 173
- References
- 6
- Language
- en
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