p(HBP:"Tau aggregates")

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Tau aggregates

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The data suggest that the increased expres- sion of AK1 can enhance tau aggregation as well as tau phos- phorylation. PubMed:22419736

MB is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Moreover, besides its beneficial properties as being able to improve energy metabolism and to act as an antioxidant, it is also able to reduce tau protein aggregation PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Other possible inhibitors of tau aggregation are rhodanine-based inhibitors, phenylthiazolyl-hydrazide inhibitors, N-phenylamines, phenothiazines and benzothiazoles, and polyphenols and anthraquinones PubMed:26751493

Recently, it has been proposed that tau protein acetylation may be responsible for tau aggregation in AD. Grinberg and collaborators detected tau acetylation at Lys274 in all tauopathies (both primary and secondary), except in AgD PubMed:26751493

Anti-tau antibodies facilitate microglial uptake of tau aggregates PubMed:29238289

Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization with Glycated derivatives appearing after 24 h. Advanced glycation end-products (AGEs) were formed during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations (day 4) indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. PubMed:19517062

In the HEK cell biosensor assay, tau from AD cases with plaques enhanced tau aggregates compared to tau from cases without plaques. In APP/PS1 cross with rTg4510 mice (P301L mutant human tau), tau seeding activity was threefold increased over the rTg4510 strain, without change in tau production or extracellular release. PubMed:28500862

Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475

Tau peptides containing phosphorylated S202, T205, and T396 were found only in Tg mice, supporting our results using AT8 and PHF1 antibodies PubMed:14642273

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

Using mass spectrometry, we identified multiple sites on recombinant tau that are phosphorylated by LRRK2 in vitro, including pT149 and pT153, which are phospho-epitopes that to date have been largely unexplored. Importantly, we demonstrate that expression of transgenic LRRK2 in a mouse model of tauopathy increased the aggregation of insoluble tau and its phosphorylation at T149, T153, T205, and S199/S202/T205 epitopes. PubMed:24113872

Our findings indicate that several acetylation sites in tau are responsive to HDAC6 and that acetylation on Lys-321 (within a KCGS motif) is both essential for acetylation-mediated inhibition of tau aggregation in vitro and a molecular tactic for preventing phosphorylation on the downstream Ser-324 residue. Tau phosphorylation of Ser-324 (pSer-324) has not previously been evaluated in the context of tauopathy, and here we observed increased deposition of pSer-324-positive tau both in mouse models of tauopathy and in patients with Alzheimer's disease. These findings uncover a novel acetylation-phosphorylation switch at Lys-321/Ser-324 that coordinately regulates tau polymerization and function. PubMed:28760828

Our findings indicate that several acetylation sites in tau are responsive to HDAC6 and that acetylation on Lys-321 (within a KCGS motif) is both essential for acetylation-mediated inhibition of tau aggregation in vitro and a molecular tactic for preventing phosphorylation on the downstream Ser-324 residue. Tau phosphorylation of Ser-324 (pSer-324) has not previously been evaluated in the context of tauopathy, and here we observed increased deposition of pSer-324-positive tau both in mouse models of tauopathy and in patients with Alzheimer's disease. These findings uncover a novel acetylation-phosphorylation switch at Lys-321/Ser-324 that coordinately regulates tau polymerization and function. PubMed:28760828

Recently, it has been proposed that tau protein acetylation may be responsible for tau aggregation in AD. Grinberg and collaborators detected tau acetylation at Lys274 in all tauopathies (both primary and secondary), except in AgD PubMed:26751493

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis PubMed:19517062

D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis PubMed:19517062

Our findings indicate that several acetylation sites in tau are responsive to HDAC6 and that acetylation on Lys-321 (within a KCGS motif) is both essential for acetylation-mediated inhibition of tau aggregation in vitro and a molecular tactic for preventing phosphorylation on the downstream Ser-324 residue. Tau phosphorylation of Ser-324 (pSer-324) has not previously been evaluated in the context of tauopathy, and here we observed increased deposition of pSer-324-positive tau both in mouse models of tauopathy and in patients with Alzheimer's disease. These findings uncover a novel acetylation-phosphorylation switch at Lys-321/Ser-324 that coordinately regulates tau polymerization and function. PubMed:28760828

In the HEK cell biosensor assay, tau from AD cases with plaques enhanced tau aggregates compared to tau from cases without plaques. In APP/PS1 cross with rTg4510 mice (P301L mutant human tau), tau seeding activity was threefold increased over the rTg4510 strain, without change in tau production or extracellular release. PubMed:28500862