Glycogen synthase kinase‐3β and tau genes interact in Alzheimer's disease

Loy, Clement T.; Hamilton, Gillian; Lau, Eric S.H.; Hallupp, Marianne; Williams, Julie; Broe, G. A.; Tang, Nelson L.S.; Lam, Linda Chiu Wa; Powell, John; Lovestone, Simon; Schofield, Peter R.

doi:10.1002/ana.21476

Cited by 70 publications

(44 citation statements)

References 40 publications

(63 reference statements)

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“…Growing evidence indicate that GSK-3 is associated with risk for human primary neurodegenerative dementias, including AD and FTDP, via interaction with Tau (Kwok et al, 2008; Schaffer et al, 2008). In the present studies, Tau expression was associated with an increase in GSK-3, but no significant differences were observed in GSK-3 activation between Tau wt and Tau P301L , suggesting that both forms of Tau may induce GSK-3 activation, perhaps leading to increased Tau hyper-phosphorylation (Cho and Johnson, 2003, 2004).…”

Section: - Discussionmentioning

confidence: 99%

RETRACTED: Wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models

Khandelwal

Dumanis

Herman

et al. 2012

Molecular and Cellular Neuroscience

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Neurodegeneration involves multiple pathogenic proteins, including Tau, Aβ, TDP-43 and α-Synuclein, but there is little information how these pathogenic proteins interact. We cloned human wild type 4 repeat Tau (Tauwt) and mutant TauP301L into a lentivirus and performed stereotaxic injection into the rat motor cortex to examine Tau modification, neuro-inflammation and changes of other proteins associated with neurodegeneration. TauP301L was associated with more phosphorylation of Tau, including Thr 181 and Ser 262 residues and resulted in more aggregation. Both forms of Tau expression increased glycogen synthase kinase-3 (GSK-3) activity, polo-like kinase-2 (PLK2) levels and decreased protein phosphatase activity, but had no effects on casein kinase-1 (CK1). No changes were observed in glial fibrillary acidic protein (GFAP) staining with either Tauwt or TauP301L, but both caused microglial changes and higher interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Tauwt and TauP301L increased the levels of endogenous α-Synuclein, but not β-amyloid precursor protein (βAPP) or Tar-DNA binding protein (TDP-43). The levels of phosphorylated Ser-129 α-Synuclein (p-Ser129) were also increased with Tauwt and TauP301L expressing animals. These data suggest that Tauwt and TauP301L alter kinase activities, but they differentially induce inflammation, Tau modification and α-Synuclein phosphorylation. This change of α-Synuclein in Tau gene transfer models suggests that Tau pathology may lead to α-Synuclein modification in neurodegenerative diseases.

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Section: - Discussionmentioning

confidence: 99%

RETRACTED: Wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models

Khandelwal

Dumanis

Herman

et al. 2012

Molecular and Cellular Neuroscience

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“…The GSK3β rs6438552 allele that was associated with reduced GM volume in our previous study (Inkster et al, 2009) alters gene transcription in vitro, leading to hyperphosphorylation of its substrate, the microtubule-associated protein tau (encoded by the gene, Mapt) (Kwok et al, 2005(Kwok et al, , 2008. Serotonergic neuronal loss has been attributed to microtubuledependent mechanisms (Ren and Feng, 2007) and lithium treatment has been shown to reduce tau phosphorylation (Hong et al, 1997).…”

Section: Discussionmentioning

confidence: 94%

Pathway-based approaches to imaging genetics association studies: Wnt signaling, GSK3beta substrates and major depression

et al. 2010

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“…It was demonstrated that the MAPT gene rs242557 polymorphism that is part of the H1c subhaplotype, results in increased MAPT gene expression [34]. The authors also provided evidence that the H1/H2 MAPT haplotype interacts with functional SNPs in the GSK3B gene to affect the risk of Alzheimer's disease.…”

Section: Tau Protein (Microtubule-associated Protein Tau Mapt)mentioning

confidence: 97%

Molecular mechanisms of neuropathological changes in Alzheimer’s disease: a review

Šerý¹,

Povová²,

Mı́šek³

et al. 2013

147

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Glycogen synthase kinase‐3β and tau genes interact in Alzheimer's disease

Cited by 70 publications

References 40 publications

RETRACTED: Wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models

RETRACTED: Wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models

Pathway-based approaches to imaging genetics association studies: Wnt signaling, GSK3beta substrates and major depression

Molecular mechanisms of neuropathological changes in Alzheimer’s disease: a review

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