p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))
To confirm the localization of ERα in NFTs, double fluorescence staining with antibodies to ERα and hyperphosphorylated tau (PHF-1) revealed that ERα -positive NFTs were also positive for PHF-1 (Fig. 2A–F). PubMed:26837465
This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926
This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926
It has been shown that activation of M1 receptors decreases tau hyperphosphorylation via activation of PKC and inhibition of GSK-3β PubMed:26813123
Possible factors such as amyloid peptide accumulation, hyperphosphorylation of tau protein, oxidative stress, and modification of cell membrane during the development of AD may be related to decreased protein levels of nAChRs (Farooqui et al 1995; Smith et al 1996) PubMed:11230871
In conjunction with the formation of neurofibrillary tangles, the synthesis of the tau protein increases, and it undergoes an abnormal posttranslational modification characterized by hyperphosphorylation PubMed:14556719
Moreover, the presence of large extracellular aggregates in NU1-treated cultures (Fig. 5N) suggests that the antibody effectively sequesters ADDLs and prevents their interactions with neurons (Fig. 5O). No inhibition of ADDL binding was associated with PP1 and LY294002 (Fig. 5H, I, K and L, respectively), but both kinase inhibitors effectively blocked ADDL-induced tau hyperphosphorylation (Fig. 5G and J). PubMed:17403556
These results confirm that the tau hyperphosphorylation stimulated by soluble ADDL preparations is indeed oligomer-induced. Tau hyperphosphorylation induced by 10M Abeta fibrils (Fig. 3N) was partially blocked (Fig. 3O), consistent with shared epitopes between oligomers and fibrils. PubMed:17403556
Importantly, pre-incubation of AD brain extracts with NU1 significantly blocked the increase in Thr231 phosphotau immunofluorescence (Fig. 6G), establishing the tau hyperphosphorylation was induced by Abeta oligomers in the AD brain extracts. NU1 also prevented the binding of brain-derived ADDLs to synaptic hot-spots (Fig. 6H and I). In NU1-treated cultures, the presence of large extracellular aggregates indicates that the antibody sequesters ADDLs and prevents their interactions with neurons (Fig. 6I). PubMed:17403556
Moreover, the presence of large extracellular aggregates in NU1-treated cultures (Fig. 5N) suggests that the antibody effectively sequesters ADDLs and prevents their interactions with neurons (Fig. 5O). No inhibition of ADDL binding was associated with PP1 and LY294002 (Fig. 5H, I, K and L, respectively), but both kinase inhibitors effectively blocked ADDL-induced tau hyperphosphorylation (Fig. 5G and J). PubMed:17403556
Inhibition occurred even though ADDLs were still bound to cell surfaces, indicating that those kinases are involved in signal transduction coupling between ADDL binding and tau hyperphosphorylation. PubMed:17403556
AD brains could induce AD-type tau hyperphosphorylation. Consistent with the results obtained with synthetic ADDLs, we found that treatment of mature hippocampal neuronal cultures with a soluble AD brain extract led to a significant increase in P231 tau phosphorylation (Fig. 6D) compared to cultures treated with a non-AD brain extract (Fig. 6A). PubMed:17403556
This model is consistent with the data that hyperphosphorylated tau appears to be specifically selected for degradation by some chaperone machines, such as the Hsp90–FKBP51 complex, without effects on normal tau [132,136]. PubMed:21882945
Hsp27 has emerged as a potential target for tau regulation based on early findings that it preferentially binds to phosphorylated and hyperphosphorylated tau and promotes their clearance [125,126] PubMed:21882945
The Hsp90 N-terminal domain inhibitor, EC102, was used to demonstrate degradation of hyperphosphorylated pathologically relevant tau in cells (Dickey et al., 2007a). PubMed:29311797
Previous studies have shown that Hsp90 inhibition decreased the levels of hyperphosphorylated and/or mutated tau species both in cells and mice. PubMed:29311797
For example, ongoing inflammation can trigger various cell stress-response pathways, including overexpression of the secreted glycoprotein Dickopff-1 (DKK-1). DKK-1 up-regulates GSK-3β activity, promotes tau hyper-phosphorylation, NFT formation and neuronal degeneration. Thus, DKK-1 inhibits Wnt signalling in a manner similar to Aβ, and thereby fosters a self-sustaining feedback loop resulting in cellular injury PubMed:18494933
In the present study, we tested the potential of two selective HDAC6 inhibitors, tubastatin A and ACY-1215, to rescue cognitive deficits in a mouse model of AD. We found that both tubastatin A and ACY-1215 alleviated behavioral deficits, altered amyloid-β (Aβ) load, and reduced tau hyperphosphorylation in AD mice without obvious adverse effects. Our data suggested that tubastatin A and ACY-1215 not only promoted tubulin acetylation, but also reduced production and facilitated autophagic clearance of Aβ and hyperphosphorylated tau. PubMed:24844691
In this study, we demonstrated that GLP-1RA could inhibit oxidative stress and repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with AGEs. Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1μg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3β (GSK-3β) to reverse tau hyperphosphorylation directly. PubMed:25987199
>8 phosphates per tau molecules (vs 2 in adult healthy brain); can also be increased during development, hibernation and temperature, heat and oxydative stress These phosphorylated states are detected by specific antibodies and are targets of proline-directed kinases (SP motifs), non-proline kinases (KXGS motif) Weakens tau-MT interaction especially S261 in R1 and S214 in proline-rich domain PubMed:8226987
>8 phosphates per tau molecules (vs 2 in adult healthy brain); can also be increased during development, hibernation and temperature, heat and oxydative stress These phosphorylated states are detected by specific antibodies and are targets of proline-directed kinases (SP motifs), non-proline kinases (KXGS motif) Weakens tau-MT interaction especially S261 in R1 and S214 in proline-rich domain PubMed:8226987
In primary neurons, overexpression of miR-125b causes tau hyperphosphorylation and an upregulation of p35, cdk5, and p44/42-MAPK signaling. In parallel, the phosphatases DUSP6 and PPP1CA and the anti-apoptotic factor Bcl-W are downregulated as direct targets of miR-125b. Knockdown of these phosphatases induces tau hyperphosphorylation, and overexpression of PPP1CA and Bcl-W prevents miR-125b-induced tau phosphorylation, suggesting that they mediate the effects of miR-125b on tau. Conversely, suppression of miR-125b in neurons by tough decoys reduces tau phosphorylation and kinase expression/activity. Injecting miR-125b into the hippocampus of mice impairs associative learning and is accompanied by downregulation of Bcl-W, DUSP6, and PPP1CA, resulting in increased tau phosphorylation in vivo. Importantly, DUSP6 and PPP1CA are also reduced in AD brains. PubMed:25001178
These results are in accord with our previous study showing that Tau hyperphosphorylation is associated with a decrease in its O-GlcNAcylation level. A recent observation argues for the hypothesis that O-GlcNAcylation occurs first and that its modification reflects on the phosphorylation status. PubMed:19732809
In primary neurons, overexpression of miR-125b causes tau hyperphosphorylation and an upregulation of p35, cdk5, and p44/42-MAPK signaling. In parallel, the phosphatases DUSP6 and PPP1CA and the anti-apoptotic factor Bcl-W are downregulated as direct targets of miR-125b. Knockdown of these phosphatases induces tau hyperphosphorylation, and overexpression of PPP1CA and Bcl-W prevents miR-125b-induced tau phosphorylation, suggesting that they mediate the effects of miR-125b on tau. Conversely, suppression of miR-125b in neurons by tough decoys reduces tau phosphorylation and kinase expression/activity. Injecting miR-125b into the hippocampus of mice impairs associative learning and is accompanied by downregulation of Bcl-W, DUSP6, and PPP1CA, resulting in increased tau phosphorylation in vivo. Importantly, DUSP6 and PPP1CA are also reduced in AD brains. PubMed:25001178
We show here that ITPKB protein level was increased 3-fold in the cerebral cortex of most patients with Alzheimer's disease compared with control subjects, and accumulated in dystrophic neurites associated to amyloid plaques. In mouse Neuro-2a neuroblastoma cells, Itpkb overexpression was associated with increased cell apoptosis and increased β-secretase 1 activity leading to overproduction of amyloid-β peptides. In this cellular model, an inhibitor of mitogen-activated kinase kinases 1/2 completely prevented overproduction of amyloid-β peptides. Transgenic overexpression of ITPKB in mouse forebrain neurons was not sufficient to induce amyloid plaque formation or tau hyperphosphorylation. However, in the 5X familial Alzheimer's disease mouse model, neuronal ITPKB overexpression significantly increased extracellular signal-regulated kinases 1/2 activation and β-secretase 1 activity, resulting in exacerbated Alzheimer's disease pathology as shown by increased astrogliosis, amyloid-β40 peptide production and tau hyperphosphorylation. PubMed:24401760
Moreover, estradiol has been shown to inhibit tau hyperphosphorylation and can also modulate glycogen synthase kinase-3β (GSK-3β) activity, a kinase that is involved in tau phosphorylation. Estradiol deactivates GSK-3β by inducing its phosphorylation, thereafter reducing tau phosphorylation. PubMed:30444369
In Alzheimer's disease, inhibition of PP2A activity by SET leads to hyper phosphorylation of the Tau protein [47]. PubMed:23454242
A key function of PP2A is thought to dephosphorylate the hyperphosphorylated Tau protein PubMed:19277525
Previous investigations indicate that specific dephosphorylation of Tau appeared to be mediated by the B family of regulatory subunits PubMed:19277525
Neuronally overexpressed GSK-3β was demonstrated to hyperphosphorylate tau protein in vivo in the brain and spinal cord of double- transgenic mice (Spittaels et al., 2000) thereby reducing the amount of protein tau associated with microtubules by 50% (Spittaels et al., 2000). PubMed:12428809
Further experiments based on the injection of a PP2A inhibitor in the rat hippocampus demon- strated tau hyper-phosphorylation, and learning and memory deficits [49, 50]. PubMed:22299660
Studies in transgenic mice and in cell cultures have shown a connection between PP2A loss of function and tau hyper-phosphorylation and aggregation into PHF. PubMed:22299660
For example, Babu et al. has shown that p62−/− knockout mice have increased levels of hyperphosphorylated tau, reduction of synaptophysin and changes in short term memory compared to p62+/− [54] PubMed:29758300
Neurofibrillary tangles composed of tau proteins in a hyperphosphorylated state are rarely observed in abundance except in AD and a limited number of aging-related tauopathies. PubMed:22908190
Recently, it has been shown that soluble Ab oligomers isolated from AD cortex can induce tau hyperphosphorylation at AD-relevant epitopes and subsequent neuritic degeneration (Jin et al. 2011). PubMed:22908190
On the other hand, it has been reported that the E3 ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) binds to tau and is involved in the degradation of abnormal forms of tau, including insoluble tau and hyperphosphorylated tau, coordinately with Hsp70 (Petrucelli et al. 2004; Dickey et al. 2006). PubMed:22908190
MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931
MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931
Recent data suggest that a critical mediator of refolding or clearance of hyperphosphorylated tau is via the HSP70/HSP90 heat shock pathways in which a specific E3 ubiquitin ligase, CHIP (carboxy terminus Hsp70 interacting protein), can recognize and target for degradation abnormal but not normal tau molecules [14–16]. PubMed:25374103
Recent data suggest that a critical mediator of refolding or clearance of hyperphosphorylated tau is via the HSP70/HSP90 heat shock pathways in which a specific E3 ubiquitin ligase, CHIP (carboxy terminus Hsp70 interacting protein), can recognize and target for degradation abnormal but not normal tau molecules [14–16]. PubMed:25374103
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763
Hippocampal neurons of Tg Tau P301S mice exhibit a high level of tau hyperphosphorylation (Fig. 4b) as well as an accumulation of pathogenic tau conformers (MC1, not shown) compared to WT littermates (Fig. 4a). PubMed:28877763
Cortical neurons of Tg Tau P301S mice also exhibit an increased level of tau hyperphosphorylation (Fig. 5b) compared to wild-type littermates (Fig. 5a). PubMed:28877763
Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763
Furthermore, N‑glycosylation may facilitate tau hyperphosphorylation, as it suppresses the dephosphorylation and accelerates the phosphorylation of tau, probably because it changes the conformation of tau PubMed:26631930
In AD, the O‑GlcNAcylation of tau is reduced — an effect that might contribute to the hyperphosphorylation and aggregation of tau PubMed:26631930
The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930
Third, the phosphorylation of tau is often considered to enhance tau aggregation, as hyperphosphorylation and aggregation are both increased in AD PubMed:26631930
AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation in rats [10]. PubMed:27288790
Higher levels of ROS biomarkers are characteristic of AD patients in clinical and preclinical studies, resulting in the alteration of membrane proper- ties, such as fluidity, ion transport, enzyme activities, protein cross- linking, tau protein hyperphosphorylation, autophagic dysfunction and eventually neuron cell death [20]. PubMed:27288790
Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532
Again, rapamycin and rapalogs protect against toxicity produced by a number of misfolded proteins encompassing alpha synuclein, TDP43, and hyperphosphorylated tau PubMed:30061532
Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532
For instance, an increased mTOR activity correlates with accumulation of Abeta and hyperphosphorylated tau in AD brains PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
In addition, most DLB patients show most features of AD (i.e., hyperphosphorylated tau deposits and A beta) to various extents PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
To confirm the localization of ERα in NFTs, double fluorescence staining with antibodies to ERα and hyperphosphorylated tau (PHF-1) revealed that ERα -positive NFTs were also positive for PHF-1 (Fig. 2A–F). PubMed:26837465
This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926
This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926
Possible factors such as amyloid peptide accumulation, hyperphosphorylation of tau protein, oxidative stress, and modification of cell membrane during the development of AD may be related to decreased protein levels of nAChRs (Farooqui et al 1995; Smith et al 1996) PubMed:11230871
AD brains could induce AD-type tau hyperphosphorylation. Consistent with the results obtained with synthetic ADDLs, we found that treatment of mature hippocampal neuronal cultures with a soluble AD brain extract led to a significant increase in P231 tau phosphorylation (Fig. 6D) compared to cultures treated with a non-AD brain extract (Fig. 6A). PubMed:17403556
However, hyperphosphorylated forms of tau are more prone to aggregate, which might decrease their solubility and remove them from normal cycling PubMed:21882945
The HMW tau species from the AD brain were highly phosphorylated compared with those from control brain (Fig. 6m). PubMed:26458742
Phosphatase treatment dephosphorylated tau in rTg4510 brain extract (Fig. 7d) without changing HMW tau levels (Fig. 7e), resulting in a significant reduction of cellular uptake of tau (Fig. 7f). PubMed:26458742
We show here that ITPKB protein level was increased 3-fold in the cerebral cortex of most patients with Alzheimer's disease compared with control subjects, and accumulated in dystrophic neurites associated to amyloid plaques. In mouse Neuro-2a neuroblastoma cells, Itpkb overexpression was associated with increased cell apoptosis and increased β-secretase 1 activity leading to overproduction of amyloid-β peptides. In this cellular model, an inhibitor of mitogen-activated kinase kinases 1/2 completely prevented overproduction of amyloid-β peptides. Transgenic overexpression of ITPKB in mouse forebrain neurons was not sufficient to induce amyloid plaque formation or tau hyperphosphorylation. However, in the 5X familial Alzheimer's disease mouse model, neuronal ITPKB overexpression significantly increased extracellular signal-regulated kinases 1/2 activation and β-secretase 1 activity, resulting in exacerbated Alzheimer's disease pathology as shown by increased astrogliosis, amyloid-β40 peptide production and tau hyperphosphorylation. PubMed:24401760
Overexpressed tau was hyperphosphorylated and resulted in decreased MT density and greater fragmentation. Using genetic screen, a histone deacetylase 6 (HDAC6) null mutation rescued tau-induced MT defects in both muscles and neurons. Genetic and pharmacological inhibition of the tubulin-specific deacetylase activity of HDAC6 indicates that the rescue effect may be mediated by increased MT acetylation. PubMed:23487739
These results are in accord with our previous study showing that Tau hyperphosphorylation is associated with a decrease in its O-GlcNAcylation level. A recent observation argues for the hypothesis that O-GlcNAcylation occurs first and that its modification reflects on the phosphorylation status. PubMed:19732809
Upon hyperphosphorylation, the protein Tau has a strong tendency to polymerize into neurofibrillary tangles in the brain, a hallmark of Alzheimer’s disease PubMed:19277525
The excessive accumulation of phosphate groups in tau is associated with its altered capacity in promoting microtubule assembly and stability [4-6]. PubMed:22299660
Studies in transgenic mice and in cell cultures have shown a connection between PP2A loss of function and tau hyper-phosphorylation and aggregation into PHF. PubMed:22299660
While misfolding of Aβ peptide and hyperphosphorylation of tau are recognized as pathogenic mechanisms of AD, accumulation of α-synuclein, which is recognized more as a risk factor for Parkinson’s disease (PD), also plays a pathological role in AD [29]. PubMed:29758300
However, when tau becomes hyperphosphorylated, it detaches from microtubules and aggregates, resulting in depolymerization of microtubules and formation of insoluble tau deposits [40] PubMed:29758300
However, when tau becomes hyperphosphorylated, it detaches from microtubules and aggregates, resulting in depolymerization of microtubules and formation of insoluble tau deposits [40] PubMed:29758300
However, when tau becomes hyperphosphorylated, it detaches from microtubules and aggregates, resulting in depolymerization of microtubules and formation of insoluble tau deposits [40] PubMed:29758300
Neurofibrillary tangles composed of tau proteins in a hyperphosphorylated state are rarely observed in abundance except in AD and a limited number of aging-related tauopathies. PubMed:22908190
MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931
MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931
Aberrant phosphorylation and aggregation of Tau have been linked to axonal transport problems, synaptic malfunction and degeneration (6). PubMed:22611162
Aberrant phosphorylation and aggregation of Tau have been linked to axonal transport problems, synaptic malfunction and degeneration (6). PubMed:22611162
Aberrant phosphorylation and aggregation of Tau have been linked to axonal transport problems, synaptic malfunction and degeneration (6). PubMed:22611162
Hyperphosphorylation of tau at the repeat domain reduces its microtubule binding, which may cause microtubule disassembly, leading to axonal transport deficits. PubMed:26631930
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103
Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763
Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763
First, hyperphosphorylation of tau might induce tau missorting from axons to the somatodendritic compartment, which can cause synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Third, the phosphorylation of tau is often considered to enhance tau aggregation, as hyperphosphorylation and aggregation are both increased in AD PubMed:26631930
For example, hyperphosphorylated tau but not unphosphorylated tau can interact with the kinesin-associated protein JUN N‑terminal kinase-interacting protein 1 (JIP1) and thus impair the formation of the kinesin complex,which mediates axonal transport PubMed:26631930
For instance, hyperphosphorylated tau can interact with JIP1 and thus impair the formation of kinesin complex PubMed:26631930
Notably, as aggregated tau in patients with a tauopathy or in transgenic mice invariably show hyperphosphorylation, and tau hyperphosphorylation precedes aggregation, phosphorylation has been assumed to drive tau aggregation PubMed:26631930
Hyperphosphorylation of tau at the repeat domain reduces its microtubule binding, which may cause microtubule disassembly, leading to axonal transport deficits. PubMed:26631930
Hyperphosphorylation of tau at the repeat domain reduces its microtubule binding, which may cause microtubule disassembly, leading to axonal transport deficits. PubMed:26631930
In a Drosophila melanogaster model of tauopathy, the hyperphosphorylation of tau led to the abnormal alignment and accumulation of F‑actin filaments, and thereby induced neurodegeneration PubMed:26631930
In a Drosophila melanogaster model of tauopathy, the hyperphosphorylation of tau led to the abnormal alignment and accumulation of F‑actin filaments, and thereby induced neurodegeneration PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
In addition, most DLB patients show most features of AD (i.e., hyperphosphorylated tau deposits and A beta) to various extents PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532
Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532
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