PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK‐3

Kerr, Fiona; Rickle, Annika; Nayeem, Naushaba; Brandner, Sebastian; Cowburn, Richard F.; Lovestone, Simon

doi:10.1016/j.febslet.2006.04.064

Cited by 55 publications

(33 citation statements)

References 60 publications

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“…Activation of GSK-3b promotes pro-apoptotic signaling [64]. On other hand, PTEN is a negative regulator of PI3K signaling and alters tau phosphorylation in cells by mechanisms independent of GSK-3b [65]. Our results show that both Ab1-42 and Ab25-35 peptides induce neither Akt phosphorylation nor PTEN phosphorylation after 48 h of exposure.…”

Section: Discussionmentioning

confidence: 62%

A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

et al. 2008

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Accumulation of the neurotoxic amyloid beta-peptide (Abeta) in the brain is a hallmark of Alzheimer's disease (AD). Several synthetic Abeta peptides have been used to study the mechanisms of toxicity. Here, we sought to establish comparability between two commonly used Abeta peptides Abeta1-42 and Abeta25-35 on an in vitro model of Abeta toxicity. For this purpose we used organotypic slice cultures of rat hippocampus and observed that both Abeta peptides caused similar toxic effects regarding to propidium iodide uptake and caspase-3 activation. In addition, we also did not observe any effect of both peptides on Akt and PTEN phosphorylation; otherwise the phosphorylation of GSK-3beta was increased. Although further studies are necessary for understanding mechanisms underlying Abeta peptide toxicity, our results provide strong evidence that Abeta1-42 and the Abeta25-35 peptides induce neural injury in a similar pattern and that Abeta25-35 is a convenient tool for the investigation of neurotoxic mechanisms involved in AD.

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Section: Discussionmentioning

confidence: 62%

A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

et al. 2008

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“…In accordance with these data, in vitro studies showed that over expression of wildtype PTEN reduces tau phosphorylation and aggregation indicating that PTEN protects against tau induced neurodegeneration [56,79]. Other studies failed to replicate these findings, and in contrast, reductions in the phosphorylated PTEN (inactive form) was found in some AD brains [80].…”

Section: Translational Neurosciencesupporting

confidence: 44%

PTEN: A molecular target for neurodegenerative disorders

Ismail

Ning

Al-Hayani

et al. 2012

Translational Neuroscience

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PTEN: a molecular target for neurodegeneratIve dIsorders abstract PTEN (phosphatase and tensin homologue deleted in chromosome 10) was first identified as a candidate tumour suppressor gene located on chromosome 10q23. It is considered as one of the most frequently mutated genes in human malignancies. Emerging evidence shows that the biological function of PTEN extends beyond its tumour suppressor activity. In the central nervous system PTEN is a crucial regulator of neuronal development, neuronal survival, axonal regeneration and synaptic plasticity. Furthermore, PTEN has been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Recently increased attention has been focused on PTEN as a potential target for the treatment of brain injury and neurodegeneration. In this review we discuss the essential functions of PTEN in the central nervous system and its involvement in neurodegeneration.

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“…This suggests that an increase in GSK3 activity or loss of negative regulation of GSK3 is insufficient to increase CRMP2 phosphorylation (Table 3). Similarly, phosphorylation of tau does not increase in concert with GSK3 activity [59,60]. Therefore, priming of CRMP2 by Cdk5 at Ser522 (and potentially tau at an unidentified site), prior to GSK3 phosphorylation, is a limiting factor.…”

Section: Gsk-3 and Cdk5mentioning

confidence: 94%

Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?

Soutar¹,

Thornhill²,

Cole³

et al. 2009

CAR

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Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer's disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal development and polarity, as well as in axon growth and guidance. In this mini-review, we examine what is known about CRMP2 function, how that is controlled by phosphorylation, what alterations in molecular mechanisms could lead to the abnormally high CRMP2 phosphorylation in AD, and whether this is likely to be specific to AD or occur in other forms of neurodegeneration. This will include discussion of the evidence for increased GSK3 or Cdk5 activity, for decreased phosphatase activity, or the upregulation of other CRMP2 protein kinases in AD. Importantly, we will compare the processes that may contribute to increased CRMP2 phosphorylation with those known to increase tau hyperphosphorylation in AD, and whether these are likely to be part of disease development or a useful early marker for AD.

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PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK‐3

Cited by 55 publications

References 60 publications

A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

PTEN: A molecular target for neurodegenerative disorders

Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?

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