The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index; 10 of the 24 sources its claims cite were checked for support.
Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells
Open accessAbstract
Hyperphosphorylated tau protein is the major constituent of the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions of Alzheimer's disease (AD). Hyperphosphorylation of tau is believed to be the critical event that leads to filament assembly. Identification of the responsible protein kinases is therefore a key step towards an understanding of the pathogenesis of AD. Mitogen-activated protein kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-like kinase have been shown to phosphorylate tau protein in vitro at a number of sites that are phosphorylated in PHFs. In this study, we report that transient transfection of human GSK3 beta into Chinese hamster ovary cells stably transfected with individual human tau isoforms leads to hyperphosphorylation of tau at all the sites investigated with phosphorylation-dependent anti-tau antibodies. Thus, GSK3 beta is a protein kinase that phosphorylates tau protein in intact cells.
Overview
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Written from the paper’s full text.
TL;DR
Transient expression of a constitutively active human GSK3β mutant in CHO cells stably expressing human tau increased tau phosphorylation at multiple PHF-associated sites. This extends in vitro evidence that GSK3β can phosphorylate tau to an intact-cell system.
Key findings
- Transfection of GSK3β(S9A) into CHO T40 and CHO T44 tau-expressing cells increased immunoreactivity with all phosphorylation-dependent anti-tau antibodies tested: PHF1 (Ser-396/Ser-404), T3P (Ser-396), AT270 (Thr-181), AT180 (Thr-231), and AT8 (Ser-202).
- GSK3β expression also caused a decrease in electrophoretic mobility of tau consistent with phosphorylation, while total tau amount remained unchanged by immunoblot.
- GSK3β was distributed throughout the cytoplasm and was not exclusively microtubule-associated; the c-myc-tagged protein ran at approximately 48 kDa in transfected cells.
- Attempts to make cell lines stably expressing both GSK3β and tau were unsuccessful because CHO cells did not survive high sustained GSK3β activity.
Methods
- Human GSK3β was mutated at Ser-9 to Ala to produce a constitutively active enzyme, tagged with c-myc, and subcloned into pSG5.
- The construct was transiently transfected by DEAE/dextran into CHO cells stably expressing three-repeat tau (CHO T44) or two N-terminal insert four-repeat tau (CHO T40); >95% of these cells expressed tau, while about 2–10% expressed high GSK3β levels.
- Tau phosphorylation was assessed 48 h after transfection by indirect immunofluorescence and immunoblotting with phosphorylation-dependent and phosphorylation-independent anti-tau antibodies.
Limitations
- The paper states that the model system does not represent physiological conditions and that only a subset of tau transfectants expressed GSK3β, making increased tau phosphorylation modest and difficult to quantify across transient transfections.
- The paper notes that GSK3β might have activated other kinases or inhibited phosphatases, although prior in vitro data support direct phosphorylation at many observed sites.
- Evident from the text: the study uses overexpression of a constitutively active GSK3β mutant in CHO cells rather than endogenous GSK3β, and the antibody panel samples only a limited set of phosphorylation sites.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
7 Own interpretation · 6 Own result · 4 Own method · 2 Supported so far · 2 Partly supported · 2 No full text of the sources · 1 Supported · 1 Couldn’t confirm · 1 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, without exception, these studies have been carried out in vitro.”
§ NEUROSCI ENCE > Abstract
What the sources say
- Could not verifycites [2] Drewes, 1992, Mitogen activated protein (MAP) kinase transform tau protein into an Alzheimer-like state, EMBO J. sourceExperimental — accuracy not yet measured
The indexed copy’s Full text section lists PDF page images rather than readable passages from the paper’s body. Searches for in vitro and in vivo tau phosphorylation found no passage stating that all prior studies of phosphorylation by these kinases were conducted in vitro; the reference list cannot establish the 'without exception' claim. (LLM, conf=0.75)
- Partly supportedcites [4] Goedert, 1992, p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1, FEBS Lett. sourceExperimental — accuracy not yet measured
The Introduction describes prior work in which a kinase purified from pig brain phosphorylated recombinant tau, and Methods §2.2 describes this paper’s phosphorylation assay using isolated tau and kinase. These passages support an in-vitro characterization, but the paper does not establish that every prior study of tau phosphorylation by the kinases was conducted in vitro. The indexed copy provides section labels but no page numbers for these passages. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [7] Hanger, 1992, Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localization of the kinase, Neurosci. Lett. source
- Partly supportedcites [12] Mandelkow, 1992, Glycogen synthase kinase 3 and the Alzheimer's disease-like state of microtubule-associated protein tau, FEBS Lett. sourceExperimental — accuracy not yet measured
The discussion (p. 56) says tau phosphorylation by several common kinases has been studied in vitro and that whether those modifications occur in vivo remains uncertain. It does not establish the stronger claim that every study of tau phosphorylation by the kinases in question was carried out in vitro. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [14] Paudel, 1993, Brain prolinedirected protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments, J. Biol. Chem. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mitogen-activated protein kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-1ike kinase have been shown to phosphorylate tau protein in vitro at a number of sites that are phosphorylated in PHFs.”
- Also stated in: § Abstract · plain
“These include mitogen-activated protein (MAP) kinase, glycogen synthase kinase-3 (GSK3) and neuronal cdc2-1ike kinase (or cdk5) [2,4,7,12,14].”
§ NEUROSCI ENCE > Abstract
What the sources say
- Partly supportedcites [2] Drewes, 1992, Mitogen activated protein (MAP) kinase transform tau protein into an Alzheimer-like state, EMBO J. sourceExperimental — accuracy not yet measured
The passage labeled Abstract in our indexed copy reports that MAP kinase phosphorylates tau and induces an Alzheimer-like state. It does not establish the claim for GSK3 or neuronal cdc2-like kinase (cdk5), and the passages retrieved for those terms provide no such result. The copy instead says that p34(cdc2) with cyclin A or B has only minor effects on tau phosphorylation; it does not identify p34(cdc2) as cdk5. (LLM, conf=0.85)
- Partly supportedcites [4] Goedert, 1992, p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1, FEBS Lett. sourceExperimental — accuracy not yet measured
The Discussion reports that p42 MAP kinase phosphorylates tau at sites abnormally phosphorylated in PHF tau. The Introduction also mentions other tau-phosphorylating kinases, but our copy does not identify them as GSK3 or neuronal cdc2-like kinase or establish the claimed result for those two enzymes. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [7] Hanger, 1992, Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localization of the kinase, Neurosci. Lett. source
- Partly supportedcites [12] Mandelkow, 1992, Glycogen synthase kinase 3 and the Alzheimer's disease-like state of microtubule-associated protein tau, FEBS Lett. sourceExperimental — accuracy not yet measured
The Introduction and section 3.1 support in-vitro phosphorylation of tau by MAP kinase and GSK3 and describe Alzheimer-like phosphorylation. They do not establish the claim for neuronal cdc2-like kinase (cdk5): the Introduction instead discusses cell-cycle cdc2, reporting only slight phosphorylation and no Alzheimer-like immune response. Page numbers are unavailable in our copy. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [14] Paudel, 1993, Brain prolinedirected protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using PHF1 and antibody 9El0 in double immunofluorescence studies, we observed a significant increase in PHF1 immunoreactivity in cells expressing the GSK3fl construct (Fig. 2E,F).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By indirect immunofluorescence using the c-myc MAb, GSK3fl was distributed throughout the cytoplasm of CHO cells which expressed the construct (Fig. 2A).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this study, we report that transient transfection of human GSK3fl into Chinese hamster ovary cells stably transfected with individual human tau isoforms leads to hyperphosphorylation of tau at all the sites investigated with phosphorylation-dependent anti-tau antibodies.”
- Also stated in: § GSK3I]S9Amyc: · plain
“However, transient transfection of CHO T40 and CHO T44 cells with GSK3fl resulted in increased immunoreactivity with all the phosphorylation-dependent anti-tau antibodies investigated.”
§ NEUROSCI ENCE > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § GSK3I]S9Amyc: · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, all cells that expressed GSK3fl also showed increased PHF1 staining, indicating that Ser-396 and Ser- 404 were phosphorylated by GSK3fl.”
- Also stated in: § GSK3I]S9Amyc: · hedged
“The increased phosphorylation of Ser-396 and Ser-404 in CHO T40 and CHO T44 ceils expressing GSK3fl could also be demonstrated by immunoblot analysis.”
- Also stated in: § GSK3I]S9Amyc: · boosted
“Thus, we demonstrate by both sequential immunofluorescence and immunobiotting that overexpression of GSK3fl causes increased tau phosphorylation at Ser-396 and Ser-404.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § GSK3I]S9Amyc: · hedged
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Controls included omitting either the first or second primary antibody, but using both secondary antibodies.Results from these controls showed no cross-over of staining in the channels for Texas Red or FITC.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because GSK3fl is only expressed in a fraction of the tau transfectants (about 2-10%), increased tau phosphorylation occurs only in those cells that express both GSK3fl and tau protein (Fig. 2E-L).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The amount of tau protein in GSK3fl-expressing and mock-transfected CHO T40 and CHO T44 cells remained unchanged (Fig. 3B).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since parallel studies with T14/46 showed no increased in immunoreactivity in cells expressing GSK3fl (Fig. 2C,D), significant crossover was unlikely in the double label experiments described above.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 6
- Probably not a substantial claim. 6
- The quote only partly states this claim. 2
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“They extend results obtained in vitro [7,12,14] to an in vivo model system, and indicate that GSK3fl may be involved in the phosphorylation of tau in vivo.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
What the sources say
- Not checked — no full text of the sourcecites [7] Hanger, 1992, Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localization of the kinase, Neurosci. Lett. source
- Supportedcites [12] Mandelkow, 1992, Glycogen synthase kinase 3 and the Alzheimer's disease-like state of microtubule-associated protein tau, FEBS Lett. source
The citation is attached to “results obtained in vitro,” not to the citing authors’ extension to an in vivo model. The Results (section 3.1) report that GSK3 phosphorylated tau and altered its antibody response and electrophoretic mobility, supporting the attributed in vitro finding. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [14] Paudel, 1993, Brain prolinedirected protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments, J. Biol. Chem. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings in GSK3β-transfected CHO cells are relevant to GSK3β-mediated tau phosphorylation in vivo.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Thus, phosphorylation of GSK3fl by MAP kinaseactivated protein kinase-1 and p70 $6 kinase at Ser 9 decreases its activity by 95% [17].”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
What the sources say
- Could not verifycites [17] Sutherland, 1993, Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signaling, Biochem. J. sourceExperimental — accuracy not yet measured
The indexed copy gives the 90–95% inactivation, the two kinases, and Ser-9 only in its Abstract, which cannot serve as evidence under this rubric. Searches for the activity reduction and Ser-9 found no Results or other body-text passage; the apparent full-text section contains links rather than the article text. (LLM, conf=0.70)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“By immunoblotting the c-myc MAb recognized a band with an apparent molecular mass of ap- proximately 48 kDa only in transfected CHO cells (Fig. 3A), consistent with the apparent molecular mass of recombinant GSK3fl [ 19] with an added c-myc tail.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
What the sources say
- Supportedcites [19] Woodgett, 1990, Molecular cloning and expression of glycogen synthase kinase-3/factor A, EMBO J. source
In “Expression of GSK-3 cDNAs,” the source reports a 47 kDa protein in cells transfected with GSK-3β DNA. The citation is attached to the comparison with the apparent mass of recombinant GSK-3β, not to the citing paper’s observation of a c-myc-reactive band in CHO cells. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“However, since in vitro studies [7,12,14] have demonstrated that tau can be directly phosphorylated by GSK3fl at many of the sites we observed in transfected cells, GSK3fl probably was directly responsible for the increased immunoreactivities and mobility shifts observed here.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
What the sources say
- Not checked — no full text of the sourcecites [7] Hanger, 1992, Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localization of the kinase, Neurosci. Lett. source
- Supportedcites [12] Mandelkow, 1992, Glycogen synthase kinase 3 and the Alzheimer's disease-like state of microtubule-associated protein tau, FEBS Lett. source
The Materials and Methods passage identifies several tau sites phosphorylated by GSK3, including Ser-199, Ser-202, Ser-396 and Ser-404. Figure 2 and the accompanying section report changes in antibody reactivity and an electrophoretic mobility shift after in vitro GSK3 treatment. The conclusion about the citing authors’ transfected cells is their inference, not a result attributed to this source. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [14] Paudel, 1993, Brain prolinedirected protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments, J. Biol. Chem. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phosphorylation of tau at this site caused an increase in PHF1 and T3P immunoreactivities, as well as a decrease in electrophoretic mobility relative to mock-transfected CHO T40 or CHO T44 cells and human fetal tau standards (Fig. 3C,D).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were obtained for tau phosphorylation at Thr-181, Ser-202 and Thr-231.”
- Also stated in: § GSK3I]S9Amyc: · plain
“Increased AT270 (Fig. 2G,H), AT180 (Fig. 2I,J) and AT8 (Fig. 2K,L) staining in transiently transfected CHO T40 was observed by indirect immunofluorescence.”
- Also stated in: § GSK3I]S9Amyc: · plain
“Furthermore, increased phosphorylation at these sites was also observed by immunoblotting of transfected cells (Fig. 3E,F and data not shown).”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § GSK3I]S9Amyc: · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Approximately 2-10% of cells expressed high levels of GSK3fl.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Prior studies have shown that many phosphorylated residues in PHF-tau are serines or threonines followed by a proline [1,6,8,11].”
§ NEUROSCI ENCE > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Bramblett, 1993, Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding, Neuron source
- Not checked — no full text of the sourcecites [6] Goedert, 1993, The abnormal phosphorylation of tau protein at serine202 in Alz heimer's disease recapitulates phosphorylation during development source
- Not checked — no full text of the sourcecites [8] Hasegawa, 1992, Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain, J. Biol. Chem. source
- Not checked — no full text of the sourcecites [11] Lee, 1991, A68: a major subunit of paired helical filaments and derivatized forms of normal tau, Science source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the net increase in tau phosphorylation as detected by immunoblot is modest since only a subset of the tau proteins are phosphorylated by GSK3fl.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Hyperphosphorylated tau protein is the major constituent of the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions of Alzheimer's disease (AD).”
- Also stated in: § Abstract · boosted
“The major fibrous component of the neurofibrillary lesions is the paired helical filament (PHF) which has been shown to be composed of highly phosphorylated forms of microtubuleassociated protein tau (PHF-tau).”
§ NEUROSCI ENCE > Abstract
What the sources say
- Not matchedcites [18] Trojanowski, 1993, PHFτ (A68): from pathological marker to potential mediator of neuron dysfunction and degen eration in Alzheimer's disease, Clin. Neurosci.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Abstract · boosted
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“They suffer from the inherent limitation that in vitro studies are not necessarily representative of in vivo events.”
§ NEUROSCI ENCE > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“CHO cell lines stably expressing either three-repeat tau (CHO T44) or two N-terminal insert four-repeat tau (CHO T40) were prepared as described [1] and >95% of the CHO T44 and CHO T40 cells express high levels of these tau proteins.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
What the sources say
- Not checked — no full text of the sourcecites [1] Bramblett, 1993, Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding, Neuron source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that both isoforms of tau showed similar immunoreactivities also suggests that the activity of GSK3fl in CHO cells was not isoformspecific.”
§ NEUROSCI ENCE > GSK3I]S9Amyc:
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Hyperphosphorylation of tau is the critical event leading to filament assembly.
“Hyperphosphorylation of tau is believed to be the critical event that leads to filament assembly.”
The paper relies on this without support.
Findings in GSK3β-transfected CHO cells are relevant to GSK3β-mediated tau phosphorylation in vivo.
“The model system used here does not represent physiological conditions, but we used it to further understand how the phosphorylation of tau is regulated in the normal and AD brain.”
“They extend results obtained in vitro [7,12,14] to an in vivo model system, and indicate that GSK3fl may be involved in the phosphorylation of tau in vivo.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GSK3 is a proline-directed kinase that contributes to phosphorylation of tau at serine or threonine followed by proline (i.e., SP/TP sites) [46–49]”
From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [48]
Experimental — accuracy not yet measured
Citations
Cites
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418
Self-citationMolecular cloning and expression of glycogen synthase kinase‐3/factor A.
Woodgett, J. R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07419.x · Cited by 1,362
Embi, N., Rylatt, D. B., & Cohen, P. (1980) · PubMed · Cited by 911
Sutherland, C., Leighton, I. A., & Cohen, P. (1993) · Biochemical Journal · doi:10.1042/bj2960015 · Cited by 903
Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q., & Lee, V. M. Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90057-x · Cited by 903
Self-citationGlycogen Synthase Kinase‐3 from Rabbit Skeletal Muscle
Noor, E. M. B. I., RYLATT, D. B., & Cohen, P. (1980) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1980.tb06059.x · Cited by 837
Hanger, D. P., Hughes, K., Woodgett, J. R., Brion, J.-P., & Anderton, B. H. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90774-2 · Cited by 737
Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer‐like state.
Drewes, G., Lichtenberg‐Kraag, B., Döring, F., Mandelkow, E. M., Biernat, J., Goris, J., Dorée, M., & Mandelkow, E. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05272.x · Cited by 565
Glycogen synthase kinase‐3 and the Alzheimer‐like state of microtubule‐associated protein tau
Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J., Vandenheede, J. R., & Mandelkow, E. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)81496-9 · Cited by 515
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488
Self-citation
Research works printed but not linked: 1
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Items 101–200 of 203
Targeting the Endocannabinoid System in Alzheimer's Disease
Koppel, J. L., & Davies, P. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15315 · Cited by 51
“This inhibition was associated with a reduction in activity of GSK-3 β , which has been linked to neurofibrillary tangle formation in brains of patients with AD [82].”
Schaffer, B., Wiedau‐Pazos, M., & Geschwind, D. H. (2003) · Gene · doi:10.1016/s0378-1119(02)01092-2 · Cited by 50
Propentofylline attenuates tau hyperphosphorylation in Alzheimer's Swedish mutant model Tg2576
Chauhan, N. B., Siegel, G. J., & Feinstein, D. L. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.09.014 · Cited by 50
Zhang, Z., Zhao, R., Qi, J., Wen, S., Tang, Y., & Wang, D. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22563 · Cited by 48
“We chose to test phosphorylation residues of tau at Ser (PHF1), Ser(202), and Thr(231), because these residues are targets of GSK-3b (Sperber et al., 1995) and are reportedly associated with PHF/tangles in the AD brains (Reynolds et al.”
MethodThe rise and fall of insulin signaling in Alzheimer’s disease
Chami, B., Steel, A. J., de la Monte, S. M., & Sutherland, G. T. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9806-1 · Cited by 48
Zhang, Y., Li, K., Yang, G., McBride, J. L., Bruner, S. D., & Ding, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-04154-3 · Cited by 52
Darios, F. D., Muriel, M., Escobar-Khondiker, M., Brice, A., & Ruberg, M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0060-05.2005 · Cited by 50
Tau phosphorylation and kinase activation in familial tauopathy linked to deln296 mutation
Ferrer, I., Pastor, P., Rey, M. J., Muñoz, E., Puig, B., Pastor, E., Oliva, R., & Tolosa, E. (2003) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2003.00435.x · Cited by 48
Differential Cytoskeletal Changes during Growth Cone Collapse in Response to hSema III and Thrombin
Fritsche, J., Reber, B. F. X., Schindelholz, B., & Bandtlow, C. E. (1999) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1999.0777 · Cited by 47
Peña‐Altamira, E., Petralla, S., Massenzio, F., Virgili, M., Bolognesi, M. L., & Monti, B. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00175 · Cited by 46
“Notably, GSK-3β appears to be responsible for tau hyperphosphorylation (Sperber et al., 1995), detaching tau from microtubules and inducing tau precipitation as intracellular neurofibrillary tangles (NFTs; Ferrer et al., 2002), a hallmark of AD.”
BackgroundGenetic Dissection of Alzheimer’s Disease Using Drosophila Models
Jeon, Y., Lee, J., Choi, B., Won, S.-Y., & Cho, K. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030884 · Cited by 46
Feyt, C., Kienlen‐Campard, P., Leroy, K., N’Kuli, F., Courtoy, P. J., Brion, J., & Octave, J. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501610200 · Cited by 46
Serretti, A., Benedetti, F., Mandelli, L., Calati, R., Caneva, B., Lorenzi, C., Fontana, V., Colombo, C., & Smeraldi, E. (2007) · Psychiatry Research · doi:10.1016/j.psychres.2007.06.017 · Cited by 43
Li, J., Du, Q., Li, N., Du, S., & Sun, Z. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111167 · Cited by 42
Xu, J., Sato, S., Okuyama, S., Swan, R. J., Jacobsen, M. T., Strunk, E., & Ikezu, T. (2010) · The FASEB Journal · doi:10.1096/fj.09-150144 · Cited by 43
“Accordingly, we observed enhanced tau phosphorylation at AT8 and PHF-1 sites, which are phosphorylated by GSK3 and CDK5, respectively (29, 30).”
BackgroundGSK3α, not GSK3β, drives hippocampal NMDAR‐dependent LTD via tau‐mediated spine anchoring
Draffin, J. E., Sánchez‐Castillo, C., Fernández‐Rodrigo, A., Sánchez‐Sáez, X., Ávila, J., Wagner, F. F., & Esteban, J. A. (2020) · The EMBO Journal · doi:10.15252/embj.2020105513 · Cited by 39
β‐Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway
Marwarha, G., Dasari, B., Prasanthi, J. R. P., Schommer, J., & Ghribi, O. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06929.x · Cited by 39
Insulin Resistance as a Common Link Between Current Alzheimer’s Disease Hypotheses
Alves, S. S., da Silva-Júnior, R. M. P., Servilha‐Menezes, G., Homolak, J., Šalković‐Petrišić, M., & Garcia‐Cairasco, N. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210234 · Cited by 39
“In fact, GSK-3 (cid:2) is the main kinase of tau protein, and it is able to phosphorylate at least 12 Ser/Thr of its pro-sites [321–323].”
Molecular Pathology of Alzheimer’s Disease and Related Disorders
Ginsberg, S. D., Schmidt, M. L., Crino, P. B., Eberwine, J. H., Lee, V. M. ‐., & Trojanowski, J. Q. (1999) · Cerebral cortex · doi:10.1007/978-1-4615-4885-0_17 · Cited by 38
Self-citationTau phosphorylation and assembly
Gómez‐Ramos, A., Smith, M. A., Perry, G. L., & Ávila, J. (2004) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2004-1489 · Cited by 38
Silva, N. M. L. E., Gonçalves, R. A., Boehnke, S. E., Forny‐Germano, L., Munoz, D. P., & Felice, F. G. D. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.016 · Cited by 37
Presenilin-Dependent Gamma-Secretase Activity Modulates Neurite Outgrowth
Figueroa, D. J., Morris, J. A., Ma, L., Kandpal, G., Chen, E., Li, Y., & Austin, C. P. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0447 · Cited by 37
Sodium tungstate decreases the phosphorylation of tau through GSK3 inactivation
Gómez‐Ramos, A., Domínguez, J. E., Zafra, D., Corominola, H., Gomis, R., Guinovart, J. J., & Ávila, J. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20726 · Cited by 36
“…tungstate contributes to the inactivation of GSK3, a kinase that mediates the hyperphosphorylation of tau in AD (Morishima-Kawashima et al., 1995; Sperber et al., 1995; Moreno et al., 1996), we propose that this compound is a good potential candidate for a new therapeutic approach to treat AD…”
BackgroundAssociation of Neurofilament Proteins with Neuronal Cdk5 Activator
Qi, R. Z., Tang, D., Zhu, X., Fujita, D. J., & Wang, J. H.-C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.2329 · Cited by 36
Molecular targets of lithium action
Corbella, B., & Vieta, E. (2003) · Acta Neuropsychiatrica · doi:10.1046/j.1601-5215.2003.00049.x · Cited by 35
Leroy, K., Menu, R., Conreur, J.-L., Dayanandan, R., Lovestone, S., Anderton, B. H., & Brion, J. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01720-2 · Cited by 34
Re-Evaluating the Role of Frat in Wnt-Signal Transduction
van Amerongen, R., & Berns, A. J. M. (2005) · Cell Cycle · doi:10.4161/cc.4.8.1886 · Cited by 34
Park, H., Lee, Y., & Chang, K. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.66604 · Cited by 33
“Additionally, GSK-3β phosphorylates the tau protein at multiple sites in intact cells [21].”
BackgroundAdvances in the development of kinase inhibitor therapeutics for Alzheimer's disease
Savage, M. J., & Gingrich, D. E. (2009) · Drug Development Research · doi:10.1002/ddr.20287 · Cited by 33
“, 1997], in transfected cell systems [Paudel, 1997; Patrick et al., 1999; Sperber et al., 1995; Hong et al., 1997; Lovestone et al., 1999; Li et al., 2006], and in animal models.”
Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis
Mondragón‐Rodríguez, S., Salgado, H., & Peña‐Ortega, F. (2020) · Neural Plasticity · doi:10.1155/2020/2960343 · Cited by 34
Fukunaga, K., Uehara, F., Aritomo, K., Shoda, A., Hiki, S., Okuyama, M., Usui, Y., Watanabe, K., Yamakoshi, K., Kohara, T., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.09.020 · Cited by 35
Canu, N., & Calissano, P. (2003) · The Cerebellum · doi:10.1080/14734220310004289 · Cited by 32
Khan, I., Tantray, M. A., Hamid, H., Alam, M. S., Kalam, A., Hussain, F., & Dhulap, A. (2016) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2016.07.007 · Cited by 31
“GSK-3 is thought to be one of the key enzymes for aberrant phosphorylation of other proteins such as the type-II regulatory subunit of cAMP-dependent protein kinase, inhibitor-2 and tau protein [4,7].”
Background6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3β inhibitors
Uehara, F., Shoda, A., Aritomo, K., Fukunaga, K., Watanabe, K., Ando, R., Shinoda, M., Ueno, H., Kubodera, H., Sunada, S., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.09.021 · Cited by 29
Identification of Peripherin as a Akt Substrate in Neurons
Konishi, H., Namikawa, K., Shikata, K., Kobatake, Y., Tachibana, T., & Kiyama, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611703200 · Cited by 27
Current strategies for the treatment of Alzheimer’s disease and other tauopathies
Dickey, C. A., & Petrucelli, L. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.5.665 · Cited by 24
“Tau kinase antagonists have attracted considerable interest and hold substantial therapeutic promise because hyperphosphorylation of tau results in its dissociation from microtubules and is associated with tau aggregation into paired helical filaments [68-73].”
BackgroundMechanism-based treatments for Alzheimer's disease
Davies, P., & Koppel, J. L. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.2/pdavies · Cited by 23
Affuso, F., Micillo, F., & Fazio, S. (2024) · Biomedicines · doi:10.3390/biomedicines12081888 · Cited by 25
“Tau is hyperphosphorylated by Increased activation of GSK3 β has been observed during brain IR [84]. glicogensynthethase kinase 3 beta (GSK3 β ), a kinase modulated by Another leading role in AD is played by apolipoprotein E (APOE), which is produced primarily by astrocytes or by neurons under…”
BackgroundGuerra‐Araiza, C., Neri-Gómez, T., Espinosa‐Raya, J., Díaz-Cintra, S. Y., Segura-Uribe, J. J., Orozco-Suárez, S. A., & Gallardo, J. M. (2017) · Neural Regeneration Research · doi:10.4103/1673-5374.205098 · Cited by 21
“Co-transfection of Tau with GSK3β elevates GSK3β activity in fibroblast cells, so as to phosphorylate Tau (Lovestone et al., 1994; Sperber et al., 1995).”
BackgroundDelobel, P., Flament, S., Hamdane, M., Delacourte, A., Vilain, J., & Buée, L. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02525-5 · Cited by 22
Irving, N. G., & Miller, C. C. J. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)13343-2 · Cited by 20
Pathogenic Factors in Vascular Dementia and Alzheimer’s Disease
Engelberg, H. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000080034 · Cited by 19
Kobro‐Flatmoen, A., Battistin, C., Nair, R. R., Bjorkli, C., Skender, B., Kentros, C. G., Gouras, G. K., & Witter, M. P. (2023) · Brain Communications · doi:10.1093/braincomms/fcad115 · Cited by 17
“Another crucial role of GSK3β is as one of the main kinases that phosphorylates tau.(56) Of direct relevance to this are studies showing that an interaction with Aβ impairs the signalling-capacity of reelin, which impairs the inhibitory control exerted by reelin-signalling upon the activity of GSK3β.”
BackgroundWang, X., Zhang, S.-G., Zhang, Y., Di, Q., Shi, J., Qian, M., Xu, L.-G., Lin, X., & Lu, J. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.184500 · Cited by 18
“…Protein Kinase I, is a proline-directed serine/threonine kinase, which phosphorylates tau at a number of AD-relevant epitopes in vitro and in transfected cells (Hanger et al., 1992; Ishiguro et al., 1992, 1993; Mandelkow et al., 1992; Mulot et al., 1994; Sperbera et al., 1995; Bass et al., 2015).”
BackgroundKhan, I., Tantray, M. A., Hamid, H., Alam, M. S., Kalam, A., Shaikh, F., Shah, A. K., & Hussain, F. (2015) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12710 · Cited by 16
“Glycogen synthase kinase-3 (GSK-3) is a serine–threonine kinase that is involved in many physiological processes such as metabolism, celldivision cycle, apoptosis, transcription, neurotransmission, insulin action and gene expression (1).”
BackgroundEmerging Targets of the GnRH Receptor: Novel Interactions with Wnt Signalling Mediators
Gardner, S., & Pawson, A. J. (2008) · Neuroendocrinology · doi:10.1159/000165377 · Cited by 17
Discovery of Compounds That Will Prevent Tau Pathology
Kosik, K. S., Ahn, J. S., Stein, R. L., & Yeh, L.-A. (2002) · Journal of Molecular Neuroscience · doi:10.1385/jmn:19:3:261 · Cited by 16
Jester, H. M., Gosrani, S. P., Ding, H., Zhou, X., Ko, M., & Ma, T. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215303 · Cited by 15
FRAT1 peptide decreases Aβ production in swAPP751 cells
Li, B., Ryder, J. W., Yuan, S., Zhou, Y., Liu, F., & Ni, B. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01042-1 · Cited by 15
Gómez‐Ramos, A., Abad, X., Fanárraga, M. L., Bhat, R. V., Zabala, J. C., & Ávila, J. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.071 · Cited by 15
Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells
Robbins, M. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.373670 · Cited by 16
Inbar, D., Belinson, H., Rosenmann, H., & Michaelson, D. M. (2010) · Neurodegenerative Diseases · doi:10.1159/000283477 · Cited by 14
Zaki, M. O., El-Desouky, S., Elsherbiny, D. A., Salama, M., & Azab, S. S. (2022) · Inflammopharmacology · doi:10.1007/s10787-022-01023-w · Cited by 12
Retractedda Rocha, A. M., Ding, J., Slawny, N. A., Wolf, A. M., & Smith, G. D. (2015) · Biology of Reproduction · doi:10.1095/biolreprod.115.128181 · Cited by 12
“Isoforms of GSK3 regulate several physiologic processes, and their dysregulation are proposed to be involved with pathogenesis of numerous diseases through divergent mechanisms of actions regulating the phosphorylation of substrates such as glycogen synthase [10], beta-catenin [11, 12], neuronal kinesin [13], tau prot…”
BackgroundGanai, S. A., Suma Mohan, S., & Padder, S. A. (2025) · Scientific Reports · doi:10.1038/s41598-025-85868-5 · Cited by 14
Turnbull, M. T., & Coulson, E. J. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160805 · Cited by 11
“BDNF deprivation of cultured mouse hippocampal neurons can cause increased tau hyperphosphorylation due to increased Akt and glycogen synthase kinase-3 (cid:2) (GSK3 (cid:2) ) activity [22], the latter being a major tau kinase and a target of BDNF-mediated signaling [23, 24].”
Usui, Y., Uehara, F., Hiki, S., Watanabe, K., Tanaka, H., Shouda, A., Yokoshima, S., Aritomo, K., Adachi, T., Fukunaga, K., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.06.078 · Cited by 12
PKCα Isoform Inhibits Insulin Signaling and Aggravates Neuronal Insulin Resistance
Mishra, D., Reddy, I., & Dey, C. S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03486-6 · Cited by 10
Russ, C., Lovestone, S., & Powell, J. F. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000941 · Cited by 10
Gentles, R. G., Hu, S., & Dubowchik, G. M. (2009) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(09)04401-7 · Cited by 10
Apoptotic action of E2F1 requires glycogen synthase kinase 3‐β activity in PC12 cells
Espada, L., Udapudi, B., Podlesniy, P., Fabregat, I., Espinet, C., & Tauler, A. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04686.x · Cited by 10
Control of transferrin expression by β‐amyloid through the CP2 transcription factor
Jang, S., Kim, J., Kim, C., An, J., Kang, E., Kim, C. G., Kim, H., & Choi, K. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07801.x · Cited by 9
Bele, M. S., Gajare, K. A., & Deshmukh, A. A. (2015) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-015-9867-1 · Cited by 9
“In vivo and in vitro studies demonstrated a positive correlation between GSK3β activity and tau phosphorylation and thus a role of GSK3β in neurodegeneration (Lovestone et al. 1994; Moreno et al. 1995; Sperber et al. 1995; Engel et al. 2008).”
BackgroundPeterson, M. F., Martin, W. H., Spencer, R. W., et al. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4126 · Cited by 7
Common Polymorphisms in the GSK3 β Gene May Contribute to the Pathogenesis of Alzheimer Disease
Lin, Q., Cao, Y., & Gao, J. (2014) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988714554712 · Cited by 6
“The inclusion of studies depended on the evaluation of the quality of study design, content, and ease of use.(22) Three broad perspectives were judged, (1) patient selection: 0*4, (2) patient comparability: 0*2, and (3) clinical outcome: 0*3.”
BackgroundAnatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice
Paris, D. (2014) · Brain Disorders & Therapy · doi:10.4172/2168-975x.1000126 · Cited by 6
In vivo and ex vivo analyses of amyloid toxicity in the Tc1 mouse model of Down syndrome
Naert, G., Ferré, V. M., Keller, E., Slender, A., Gibbins, D., Fisher, E., Tybulewicz, V. L. J., & Maurice, T. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117743484 · Cited by 5
How does lithium mediate its therapeutic effects?
Strunecká, A., Patočka, J., & Šárek, M. (2005) · Journal of Applied Biomedicine · doi:10.32725/jab.2005.003 · Cited by 6
“GSK-3 β isoform can phosphorylate protein τ (Sperber et al. 1995).”
BackgroundThe Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer’s Disease
Schulz, J. M. (2021) · Stem Cells International · doi:10.1155/2021/5511630 · Cited by 6
Süer, C., Demircan, N. Y., Barutçu, Ö., Tan, B., & Dursun, N. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00254-y · Cited by 5
Development of Neuronal Polarity In Vivo
Polleux, F. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397266-8.00123-x · Cited by 5
Targeting the GSK3β/β-catenin Signaling to Treat Alzheimer´s Disease: Plausible or Utopic?
Zeidán‐Chuliá, F., & Moreira, J. C. F. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50014-3 · Cited by 3
The role of glycogen synthase kinase‐3 inhibitors on bone remodeling
Escott, K. J., & O'Shea, P. J. (2016) · doi:10.1002/9781118907474.ch13 · Cited by 3
τ Protein and the Neurofibrillary Pathology of Alzheimer’s Disease
Goedert, M., Trojanowski, J. Q., & Lee, V. M. ‐. (1997) · Humana Press eBooks · doi:10.1007/978-1-59259-471-9_12 · Cited by 3
Self-citationPin1 Protects Against Alzheimer's Disease: One Goal, Multiple Mechanisms
Pastorino, L., Kondo, A., Zhen, X., & Lu, K. P. (2013) · InTech eBooks · doi:10.5772/55085 · Cited by 2
Kurkó, D., Boros, A. M., Dezső, P., Urbányi, Z., Sárvári, M., Nagy, J., Szombathelyi, Z., & Szendrei, G. I. (2006) · Neurochemistry International · doi:10.1016/j.neuint.2005.11.010 · Cited by 2
A mitotic role for GSK‐3β kinase in Drosophila
Wojcik, E. J. (2009) · The FASEB Journal · doi:10.1096/fasebj.23.1_supplement.659.2 · Cited by 2
Bhargavan, B., Annadurai, N., & Kanmogne, G. D. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02197-4 · Cited by 1
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Salinas, P. C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397266-8.00106-x · Cited by 1
Alzheimer’s Disease: What Do We Know About It and How Can We Tackle It?
Mirpuri, B. (2022) · International journal of high school research · doi:10.36838/v4i2.13
Drosophila and C. elegans Models of Human Age-Associated Neurodegenerative Diseases
Bilen, J., & Bonini, N. M. (2007) · Springer eBooks · doi:10.1007/0-387-25919-8_18 · Cited by 1
Lovestone, S. (1996) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(199604)11:4 · Cited by 1
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Self-citationMetabolic Abnormalities in Alzheimer Disease
Gebhardt, F. M., & Dodd, P. R. (2008) · Springer eBooks · doi:10.1007/978-0-387-79112-8_22 · Cited by 1
Etude de la régulation de deux protéines kinases : GSK-3 et polo
Primot, A. (2001) · HAL
Tran, H. (2011) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7gb223z
Measuring molecular motor forces to probe transport regulation in vivo
Leidel, C. (2012) · Texas ScholarWorks (Texas Digital Library)
Kvantitatív PCR alkalmazása a gyógyszerkutatásban
Nagy, J. (2007)
da Rocha, A. M., Ding, J., Slawny, N. A., Wolf, A. M., & Gary, D. (2016)
Croft, C. L. (2016) · Research Portal (King's College London)
Pathological Tau as a Cause, and Consequence, of Cellular Dysfunction
Meier, S. E. (2019) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2019.368
“GSK3β is a major tau kinase [370] that is known to phosphorylate tau at the epitopes detected by AT8 [371].”
InfluentialAutophagic Dysfunction in Neurodegeneration
Kaira, M., Ahlawat, A., Walia, V., & Garg, M. (2020) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-7998-1317-0.ch002
Jester, H. M., Gosrani, S. P., Ding, H., Zhou, X., Ko, M., & Ma, T. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.21.453246
大西, 智., & Onishi, T. (2016) · Terrestrial Environment Research Center (University of Tsukuba)
Development of neuronal polarity in vivo
Polleux, F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814407-7.00001-8
Tau Protein and the Neurofibrillary Pathology of Alzheimer’s Disease
Goedert, M. (1996) · Springer eBooks · doi:10.1007/978-3-642-80109-9_9 · Cited by 1
Self-citationHanotte, J. L. (2023) · El Servicio de Difusión de la Creación Intelectual (National University of La Plata) · doi:10.35537/10915/161150
Karati, D., Mukherjee, S., & Batabyal, N. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95735-9.00013-9
Metadata
- Authors
- Sperbera, B. R., Leight, S., Goedert, M., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Lee, V.M.-Y.
- ORCID
- Goedert, Michel
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1995-09
- Volume
- 197
- Issue
- 2
- Pages
- 149-153
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2078680897
- Semantic Scholar
- b65c92714a748a00c0908686620cc4d7ab64e748
- Cited by
- 204
- References
- 19
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroscience Letters (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- glycogen synthase kinase-3β, tau protein, tau hyperphosphorylation, paired helical filaments, Alzheimer's disease, neurofibrillary tangles, protein kinases, tau isoforms, mitogen-activated protein kinase, phosphorylation sites
- MeSH terms
- Alanine, Amino Acid Sequence, Animals, Cricetinae, Humans, Molecular Sequence Data, Mutation, Phosphorylation, Serine, Transfection, Immunoblotting, CHO Cells, tau Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Fluorescent Antibody Technique, Indirect, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-18, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-18 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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