p(HGNC:MAPT, var("p.Pro301Leu"))

Entity

Name

MAPT

Namespace

hgnc

Namespace Version

20180906

Namespace URL

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

Additionally, Aha1-specific inhibitors have been recently developed (Hall et al., 2014). One of these inhibitors, KU-177, reduced insoluble tauP301L levels in cells (Shelton et al., 2017). PubMed:29311797

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

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

The tauopathy mice that we used contained the P301L mutation, which is implicated in some genetic tauopathies. In addition, this mutation, along with the related P301S mutation, has been associated with increased inflammation in the brain as well as retinal deficits PubMed:27716675

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

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

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

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

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

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

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Messenger RNA analysis of two pro-inflammatory markers such as IL-1β and inducible nitric oxide synthase (iNOS) indicate that TAUP301L expression induce Il-1β (Fig. 6D) and iNOS (Fig. 7D) mRNA expression in both genotypes and DMF treatment decreased this expression only in Nrf2+/+ mice. PubMed:29121589

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 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

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

Astrocytes displayed enlarged bodies and ramifications (Type B morphology), consistent with a reactive state after TAUP301L expression in Nrf2+/+ and Nrf2−/− mice (Fig. 6A left panels). However, only astrocytes from Nrf2+/+ mice treated with DMF were maintained in a resting morphology (Type A) (Fig. 6A right panels). Concerning microglia, TAUP301L expression induced a very significant increase in IBA1+ microglia at the ipsilateral hippocampal side of Nrf2+/+ and Nrf2−/− mice (Fig. 7A), which was confirmed by stereological quantification (Fig. 7B). DMF treatment reduced significantly this microgliosis in Nrf2+/+ but not in Nrf2−/− mice, reinforcing the idea of NRF2-dependent anti-inflammatory effect PubMed:29121589

Astrocytes displayed enlarged bodies and ramifications (Type B morphology), consistent with a reactive state after TAUP301L expression in Nrf2+/+ and Nrf2−/− mice (Fig. 6A left panels). However, only astrocytes from Nrf2+/+ mice treated with DMF were maintained in a resting morphology (Type A) (Fig. 6A right panels). Concerning microglia, TAUP301L expression induced a very significant increase in IBA1+ microglia at the ipsilateral hippocampal side of Nrf2+/+ and Nrf2−/− mice (Fig. 7A), which was confirmed by stereological quantification (Fig. 7B). DMF treatment reduced significantly this microgliosis in Nrf2+/+ but not in Nrf2−/− mice, reinforcing the idea of NRF2-dependent anti-inflammatory effect PubMed:29121589

Messenger RNA analysis of two pro-inflammatory markers such as IL-1β and inducible nitric oxide synthase (iNOS) indicate that TAUP301L expression induce Il-1β (Fig. 6D) and iNOS (Fig. 7D) mRNA expression in both genotypes and DMF treatment decreased this expression only in Nrf2+/+ mice. PubMed:29121589

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

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

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

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

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

The tauopathy mice that we used contained the P301L mutation, which is implicated in some genetic tauopathies. In addition, this mutation, along with the related P301S mutation, has been associated with increased inflammation in the brain as well as retinal deficits PubMed:27716675

Tau protein with mutations in or near the microtubule-binding domain (for instance, G272V, N279K, ΔK280, P301L, V337M or R406W) tend to have a reduced affinity for microtubules and an increased tendency for aggregation PubMed:26631930

Tau protein with mutations in or near the microtubule-binding domain (for instance, G272V, N279K, ΔK280, P301L, V337M or R406W) tend to have a reduced affinity for microtubules and an increased tendency for aggregation PubMed:26631930

Disruption of these motifs (for example, by Pro mutations) abrogates the tendency for tau to aggregate; by contrast, strengthening the β‑structure with certain mutations (for instance, ΔK280 or P301L) accelerates tau aggregation both in vitro and in vivo PubMed:26631930

Remarkably, in two regulatable transgenic mouse models expressing human tau with the P301L mutation (rTg4510) or expressing the repeat domain of tau with the ΔK280 mutation, switching off tau expression improved memory impairment even though NFTs remained, clearly showing that tau aggregates are not sufficient for neurodegeneration and the cognitive effects that are typically observed in these models PubMed:26631930