Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51.

Novák, Michal; Jakes, Ross; Edwards, Patricia C.; Milstein, C.; Wischik, Claude M.

doi:10.1073/pnas.88.13.5837

Cited by 197 publications

(136 citation statements)

References 41 publications

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“…According to the residue numbering of the longest human tau isoform of 441 aa, antibody PHF-1 and AD2 can react with tau when serines 396 and 404 are phosphorylated (Buee-Scherrer et al, 1996), although it has also been reported that the presence of phosphorylated Ser396 in tau protein appears to be sufficient for AD2 recognition and that phosphorylation in Ser404 seems not to play a major role in this binding (Torreilles et al, 2000) and the AT-8 antibody recognizes tau when Ser202 and Thr205 are phosphorylated (Goedert et al, 1995). The 7.51 antibody recognizes segments of the last two repeats within the microtubule binding domain of tau in a phosphorylation-independent manner (Novak et al, 1991) and detects all soluble tau isoforms in Western blot analysis and unbound tau in immunohistochemical analysis.…”

Section: Methodsmentioning

confidence: 99%

“…In good agreement, we have previously shown that tau hyperphosphorylation in Tet/GSK-3␤ mice correlates with somatodendritic accumulation of microtubule-unbound tau in hippocampal neurons (Lucas et al, 2001). This was evidenced by immunohistochemistry with the 7.51 antibody that recognizes the microtubule binding domain of tau and that, accordingly, detects only unbound tau (Novak et al, 1991). We therefore decided to test whether somatodendritic accumulation of microtubuleunbound tau in hippocampal neurons of Tet/GSK-3␤ mice was also reversible after restoration of normal GSK-3 levels.…”

Section: Microtubule Binding and Stabilization Ability Of Tau Are Resmentioning

confidence: 99%

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Full Reversal of Alzheimer's Disease-Like Phenotype in a Mouse Model with Conditional Overexpression of Glycogen Synthase Kinase-3

Engel¹,

Hernández²,

Ávila³

et al. 2006

J. Neurosci.

233

182

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Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase that is particularly abundant in the CNS. Dysregulation of GSK-3 activity is believed to play a key role in the pathogenesis of CNS chronic disorders such as Alzheimer's disease (AD), bipolar disorder, and Huntington's disease, and of metabolic disorders such as type II diabetes. Accordingly, GSK-3 inhibitors have been postulated as therapeutic tools for these diseases. Interestingly, pathophysiological and pharmacological regulation of GSK-3 is affected by an amplification mechanism that applies both to inhibition and activation. The possibility therefore exists that sustained inhibition or activation might persist after cessation of the initial trigger. Regarding AD, GSK-3 has been shown to accumulate in pretangle neurons. Furthermore, GSK-3 phosphorylates tau in most serine and threonine residues hyperphosphorylated in PHF (paired helical filament)-tau and GSK-3 activity contributes both to ␤-amyloid production and to ␤-amyloid-mediated neuronal death. In good agreement, mice with conditional overexpression of GSK-3 in forebrain neurons (Tet/GSK-3␤ mice) recapitulate aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and reactive astrocytosis as well as spatial learning deficit. Here, we exploit the conditional system used to generate Tet/GSK-3␤ mice to explore whether the biochemical, histopathological, and behavioral consequences of increased GSK-3 activity are susceptible to revert after restoration of normal GSK-3 levels. Here, we show that transgene shutdown in symptomatic mice leads to normal GSK-3 activity, normal phospho-tau levels, diminished neuronal death, and suppression of the cognitive deficit, thus further supporting the potential of GSK-3 inhibitors for AD therapeutics.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Microtubule Binding and Stabilization Ability Of Tau Are Resmentioning

confidence: 99%

Full Reversal of Alzheimer's Disease-Like Phenotype in a Mouse Model with Conditional Overexpression of Glycogen Synthase Kinase-3

Engel¹,

Hernández²,

Ávila³

et al. 2006

J. Neurosci.

233

182

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“…The phosphorylation-independent Tau monoclonal antibody 7.51 (39) was kindly provided by Dr. C. M. Wischik. The monoclonal antibodies Tau-1 and Tau-5 were purchased from Chemicon International and Calbiochem, respectively.…”

Section: Methodsmentioning

confidence: 99%

Microtubule-associated Protein 1B (MAP1B) Is Required for Dendritic Spine Development and Synaptic Maturation

Tortosa

Montenegro-Venegas

Benoist

et al. 2011

Journal of Biological Chemistry

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Background: Microtubule-associated protein 1B (MAP1B) is a protein that is prominently expressed during early neuronal development but in adult brain remains in areas with high synaptic plasticity. Results: MAP1B plays an important role in dendritic spine formation and synaptic maturation. Conclusion: A novel function for MAP1B in regulating dendritic spine morphology and synaptic function is indicated. Significance: MAP1B could contribute to adult brain plasticity.

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“…It has been shown that truncation is closely associated with Alzheimer's disease (AD)-typical conformational changes of the tau protein [5][6][7][8][9][10]. We have hypothesized that truncation could play major role in AD tau pathology [11].…”

Section: Introductionmentioning

confidence: 99%

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

Žilka¹,

Filipčík²,

Koson³

et al. 2006

FEBS Letters

224

203

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Truncated tau protein is the characteristic feature of human sporadic Alzheimer's disease. We have identified truncated tau proteins conformationally different from normal healthy tau. Subpopulations of these structurally different tau species promoted abnormal microtubule assembly in vitro suggesting toxic gain of function. To validate pathological activity in vivo we expressed active form of human truncated tau protein as transgene, in the rat brain. Its neuronal expression led to the development of the neurofibrillary degeneration of Alzheimer's type. Furthermore, biochemical analysis of neurofibrillary changes revealed that massive sarcosyl insoluble tau complexes consisted of human Alzheimer's tau and endogenous rat tau in ratio 1:1 including characteristic Alzheimer's disease (AD)-specific proteins (A68). This work represents first insight into the possible causative role of truncated tau in AD neurofibrillary degeneration in vivo.

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Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51.

Abstract: Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51 (neurofibrillary tangles/neurodegeneration)

Cited by 197 publications

References 41 publications

Full Reversal of Alzheimer's Disease-Like Phenotype in a Mouse Model with Conditional Overexpression of Glycogen Synthase Kinase-3

Full Reversal of Alzheimer's Disease-Like Phenotype in a Mouse Model with Conditional Overexpression of Glycogen Synthase Kinase-3

Microtubule-associated Protein 1B (MAP1B) Is Required for Dendritic Spine Development and Synaptic Maturation

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

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