p(HGNC:MAPT, pmod(Ph, Ser, 422))

Entity

Name

MAPT

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

A quite different strategy is to target tau clearance—e.g., by rapamycin that induces macroautophagy [175], inhibitors of Hsp90 chaperone protein that binds to misfolded proteins or by immunotherapeutic approaches [176]. PubMed:26751493

3. Putative phosphorylation sites on tau protein and epitopes specific for major tau antibodies. Red color denotes amino acids phosphorylation in AD brain. PubMed:26751493

TOC1’s immunoreactivity is greatly elevated in AD brains compared with healthy controls, but co-localizes best with early-stage markers for AD pathogenesis such as pS422 [16] PubMed:22817713

These data suggest a role for TTBK1 in pre-tangle formation prior to the formation of fibrillar tau and strengthen the idea that tau is phosphorylated at Ser422 at an early intermediate stage in NFT formation. PubMed:18239272

Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. PubMed:26118667

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

Finally, phosphorylation of S422 in tau, as recognisedby antibody AP422, was generated most e¤ciently by SAPK3/p38gamma, SAPK4/p38delta and SAPK2b/p38beta PubMed:11943212

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

Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. PubMed:27373205

Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. PubMed:27373205

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

Finally, phosphorylation of S422 in tau, as recognisedby antibody AP422, was generated most e¤ciently by SAPK3/p38gamma, SAPK4/p38delta and SAPK2b/p38beta PubMed:11943212

Finally, phosphorylation of S422 in tau, as recognisedby antibody AP422, was generated most e¤ciently by SAPK3/p38gamma, SAPK4/p38delta and SAPK2b/p38beta PubMed:11943212

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

Epitopes S198, S199, S202, T205, S422 (Lund 2013) PubMed:18239272

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

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

For example, both soluble and insoluble tau from transgenic worms generated by Kraemer and colleagues (66) was phosphorylated at most of the sites examined; however, the insoluble tau did not show reactivity at the AT8 and pS422 epitopes, which are pronounced in human AD tau. PubMed:29191965

3. Putative phosphorylation sites on tau protein and epitopes specific for major tau antibodies. Red color denotes amino acids phosphorylation in AD brain. PubMed:26751493

TOC1’s immunoreactivity is greatly elevated in AD brains compared with healthy controls, but co-localizes best with early-stage markers for AD pathogenesis such as pS422 [16] PubMed:22817713

We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). These 4 markers are particularly useful in understanding potential posttraumatic events in CTE because PAD exposure impairs axonal transport (24), oligomers confer toxicity (28, 38–40), pS422 correlates with cognitive decline (15), and D421 truncated tau may be related to cell toxicity (41, 42). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. PubMed:26671985

We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). These 4 markers are particularly useful in understanding potential posttraumatic events in CTE because PAD exposure impairs axonal transport (24), oligomers confer toxicity (28, 38–40), pS422 correlates with cognitive decline (15), and D421 truncated tau may be related to cell toxicity (41, 42). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. PubMed:26671985

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

These data suggest a role for TTBK1 in pre-tangle formation prior to the formation of fibrillar tau and strengthen the idea that tau is phosphorylated at Ser422 at an early intermediate stage in NFT formation. PubMed:18239272

Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. PubMed:26118667

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. PubMed:27373205

Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. PubMed:27373205

Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. PubMed:27373205

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

For example, both soluble and insoluble tau from transgenic worms generated by Kraemer and colleagues (66) was phosphorylated at most of the sites examined; however, the insoluble tau did not show reactivity at the AT8 and pS422 epitopes, which are pronounced in human AD tau. PubMed:29191965

For instance, the phosphorylation of tau at Ser422 inhibits the cleavage of tau by caspase 3 at Asp421 PubMed:26631930