Equivalencies: 0 | Classes: 2 | Children: 0 | Explore

Appears in Networks 10

In-Edges 37

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

p(FPLX:ERK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

p(FPLX:GSK3) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

p(HGNC:CDK2) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The diagnostic antibodies AT8, TAU-1, SM131, SM134, and SM133 react to phosphorylation similarly as with MAPK and GSK-3, indicating that SP motifs before the repeat region (S199 and/or S202, S235) and after the repeats (S396, S404) become phosphorylated (Fig. 2,-2,); note that AT8, SMUl, and SM134 react with PHFs where the epitopes containing SP motifs are phosphorylated, while TAU-1 and SM133 react with normal tau where the epitopes are not phosphorylated PubMed:8282104

p(HGNC:CDK2) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Glycogen synthase 3β (GSK3β) is one of the main serine-threonine kinase responsible for tau phosphorylation and has been shown to affect tau phosphorylation at multiple AD relevant epitopes including Ser396, Ser404, Thr231 and Ser202 DOI:10.4172/2168-975X.1000126

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

path(MESH:"Alzheimer Disease") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Interestingly, the phosphorylated form of tau at Ser 396/404 (PHF-1) was detected exclusively in AD patients, although total amounts of tau protein (TG5) were not changed PubMed:22419736

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

However, the AD brain extract (3,000g) contained significantly higher levels of phosphorylated tau (Fig. 6h,i,m) when compared with the control brain, especially those associated with some specific phosphorylation sites such as pS199, pS396 and pS404 (Fig. 6i). PubMed:26458742

p(HGNC:CDC37) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Quantification of the Western blot showed that Cdc37 knockdown reduced phospho-Thr-231, phospho-Ser-199/Ser-202, phospho-Ser-396/Ser-404, and phospho-Ser-262/Ser-356 tau. PubMed:21367866

complex(p(HGNC:FKBP5), p(HGNC:MAPT)) association p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

p(HGNC:FKBP5) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

p(HGNC:GSK3B) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

These data indicated that phosphorylation of PP2A dephosphorylation sites is an important recognition signal for ubiquitination. We used 200 μg of amino-terminal His-tagged full-length recombinant human tau in an in vitro phosphorylation reaction with GSK-3Beta. When phosphorylated, the tau protein reacted on immunoblots with PHF1 (25, 26) and AT8 (24), indicating that at least sites Ser202, Thr205, Ser396, and Ser404 were phosphorylated. Following GSK-3Beta incubation, this tau served as an excellent substrate for in vitro ubiquitination using UbcH5B and the cofactor fraction from AD tau immunoprecipitates (Fig. 2a). This finding suggested that GSK-3Beta can place phosphates on tau that create recognition sites for an E3 Ub ligase. PubMed:14612456

p(HBP:"Tau isoform F (441 aa)", var("p.Arg406Tyr")) decreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The quantification of all immunoreactive bands revealed that the R406W mutation exhibits a decreased phosphorylation at T205, T212, and the PHF1 epitope (S396/S404; reductions of 40–65%) as compared with wt tau, whereas other sites were not affected or only slightly affected (T181, S199, S214, and S262). PubMed:21339331

a(CHEBI:"D-ribose") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. PubMed:26095350

Appears in Networks:

a(CHEBI:"D-ribose") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. PubMed:28176663

Appears in Networks:

a(CHEBI:Nilvadipine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Western blot analyses of brain homogenates show that (−)-nilvadipine significantly reduces Tau phosphorylation in AT8 (phosphorylated Ser-199/Ser-202/Thr-205) and PHF-1 (phosphorylated Ser-396/Ser-404) epitopes PubMed:25331948

Appears in Networks:

a(HBP:"advanced glycation end product") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Thus, our results suggest that Tau hyperphosphorylation was a result of ribosylated AGEs, rather than due to a direct reaction involving D-ribose. PubMed:28176663

Appears in Networks:

a(HBP:"Tau epitope, PHF1") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

We first confirmed that expression of an MKI-GFP fusion protein in rat hippocampal neurons effectively attenuated MARK4-mediated phosphorylation of both endogenous tau (Fig. 3A) and transfected human tau at the 12E8 sites (Fig. 3B). Phosphorylation of tau at the PHF-1 site was also reduced by MKI (Fig. 3A). It is possible that the PHF-1 site is also targeted by PAR-1/MARKs in vivo, or that the phosphorylation of tau at the 12E8 sites is a prerequisite for PHF-1 site phosphorylation, as the 12E8 sites were previously shown to be required for tau phosphorylation at other sites PubMed:22156579

Appears in Networks:

a(HBP:MPT0G211) decreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment. PubMed:29844403

Appears in Networks:

bp(GO:"apoptotic process") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

Appears in Networks:

p(FPLX:PKA) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

p(HGNC:DAPK1) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

As shown in Figure 7a, compared with the vector control, DAPK1, but not DAPK1K42A, increased the phosphorylation of exogenous tau protein in HeLa cells, as detected by Thr231-specific (AT180), Ser262-specific, and Ser396-specific (PHF-13) antibodies that recognize specific tau phosphoepitopes and/or abnormal conformations specific to AD NFT. PubMed:24853415

Appears in Networks:

p(HGNC:DAPK1) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

Appears in Networks:

act(p(HGNC:GSK3B), ma(kin)) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:GSK3B), ma(kin)) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Because S199/S202/T205E, S396/S404E, 6-Phos and 7-Phos all demonstrated an AD-like shift in mobility as a result of phosphorylation-like changes, we conclude that they have the characteristics of hyperphosphorylated tau. These mutants will therefore be referred to as pseudo-hyperphosphorylated tau throughout the manuscript. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation. PubMed:19459590

Appears in Networks:

act(p(HGNC:GSK3B)) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment. PubMed:29844403

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. PubMed:22833681

Appears in Networks:

a(CHEBI:"okadaic acid") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

p(HGNC:MAPT, var("p.Val277Met")) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

In add- ition, only FL Tau V337M was phosphorylated at the KXGS motif (Fig. 2A, mid panel, 12E8), S396 and S404 (PHF-1 epitope) (Fig. 2A, lower panel, PHF-1). PubMed:22611162

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

p(HGNC:GSK3B) increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

Out-Edges 16

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

However, the AD brain extract (3,000g) contained significantly higher levels of phosphorylated tau (Fig. 6h,i,m) when compared with the control brain, especially those associated with some specific phosphorylation sites such as pS199, pS396 and pS404 (Fig. 6i). PubMed:26458742

p(HGNC:MAPT, pmod(Ph, Ser, 396)) association complex(p(HGNC:FKBP5), p(HGNC:MAPT)) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation p(HGNC:FKBP5) View Subject | View Object

We found that FKBP51 indeed could interact with tau from both AD patients and control cases (Fig. 3D), further suggesting a functionally relevant relationship between FKBP51 and tau. We then investigated whether FKBP51 would preferentially interact with phosphorylated tau species. We increased the number of samples per group (4 for AD and 4 for normal) and again co-immunoprecipitated FKBP51. After gel electrophoresis, immunoblotting showed increased association of pS396 and pS199-S202 tau species with FKBP51 in AD tissue (Fig S1). Indeed, we found that FKBP51 over-expression increased phospho- and total tau levels (by 80%) in HeLa cells stably expressing normal human tau, while FKBP52 over-expression had no affect (Fig.4A). These experiments were repeated multiple times and Student t-test of these replicates demonstrated that FKBP51 significantly increased total tau levels (p= 0.0104). PubMed:20071522

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation p(HGNC:CDC37) View Subject | View Object

Quantification of the Western blot showed that Cdc37 knockdown reduced phospho-Thr-231, phospho-Ser-199/Ser-202, phospho-Ser-396/Ser-404, and phospho-Ser-262/Ser-356 tau. PubMed:21367866

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation p(FPLX:PKA) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation a(HBP:"Tau epitope, PHF1") View Subject | View Object

We first confirmed that expression of an MKI-GFP fusion protein in rat hippocampal neurons effectively attenuated MARK4-mediated phosphorylation of both endogenous tau (Fig. 3A) and transfected human tau at the 12E8 sites (Fig. 3B). Phosphorylation of tau at the PHF-1 site was also reduced by MKI (Fig. 3A). It is possible that the PHF-1 site is also targeted by PAR-1/MARKs in vivo, or that the phosphorylation of tau at the 12E8 sites is a prerequisite for PHF-1 site phosphorylation, as the 12E8 sites were previously shown to be required for tau phosphorylation at other sites PubMed:22156579

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) negativeCorrelation bp(GO:"apoptotic process") View Subject | View Object

These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration. PubMed:23948915

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation a(CHEBI:"D-ribose") View Subject | View Object

Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. PubMed:28176663

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau. PubMed:22833681

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation act(p(HGNC:GSK3B)) View Subject | View Object

This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment. PubMed:29844403

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Similar findings have been observed in metabolically active rat brain slices, where a selective inhibition of PP2A with OA results in an aberrant phosphorylation of tau at the same residues seen in AD brains at serines (Ser) 198, 199, 202, 396, 404, 422 and 262 [11, 47, 48]. PubMed:22299660

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.