p(HGNC:MAPT, var("p.Ala152Thr"))
For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300
Another MAPT polymorphism (A152T) was recently identified in patients diagnosed with progressive supranuclear palsy (PSP) (72–74). PubMed:29191965
Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930
Four weeks after terminal differentiation, 80% of cells were positive for the neuron-specific marker MAP2, and there was no significant difference between control and patient neurons (Figure S2A) PubMed:27594586
The percentages of VGLUT1-positive excitatory and GABA-positive inhibitory neurons were similar in neuronal cultures differentiated from control and patient iPSCs (Figures S2B and S2C) PubMed:27594586
The percentages of VGLUT1-positive excitatory and GABA-positive inhibitory neurons were similar in neuronal cultures differentiated from control and patient iPSCs (Figures S2B and S2C) PubMed:27594586
Moreover, the total expression levels of tau and PSD-95 were the same in 1-month-old neurons derived from control and patient iPSCs (Figure 1B) PubMed:27594586
Moreover, the total expression levels of tau and PSD-95 were the same in 1-month-old neurons derived from control and patient iPSCs (Figure 1B) PubMed:27594586
The resting membrane potential did not differ among neurons differentiated from all iPSC lines (Figure S2D) PubMed:27594586
Thus, both molecular and electrophysiological analyses suggest MAPT mutations do not affect early neuronal differentiation PubMed:27594586
Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586
Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586
The level of secreted MMP-9 and MMP-2 was also increased in cortical neurons derived from a published iPSC line with the tau-A152T mutation (Fong et al., 2013) (Figures 2E and 2F) PubMed:27594586
It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586
It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586
The level of secreted MMP-9 and MMP-2 was also increased in cortical neurons derived from a published iPSC line with the tau-A152T mutation (Fong et al., 2013) (Figures 2E and 2F) PubMed:27594586
It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586
It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586
This increase is likely in part due to transcriptional regulation, since the mRNA levels of MMP-9 and MMP-2 in tau-A152T and MAPT IVS10+16 neurons were higher than in control neurons (Figure S2J) PubMed:27594586
MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586
This increase is likely in part due to transcriptional regulation, since the mRNA levels of MMP-9 and MMP-2 in tau-A152T and MAPT IVS10+16 neurons were higher than in control neurons (Figure S2J) PubMed:27594586
MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586
We found that, indeed, TUJ1+ neurons showed reduced survival as measured by TUNEL analysis (Figure 3A) PubMed:27594586
The level of phosphorylated ERK (p-ERK) was significantly increased in tau-A152T neurons and to a lesser extent in MAPT IVS10+16 patient neurons (Figure 4A) PubMed:27594586
Interestingly, this ratio is also increased, but to a lesser extent, in tau-A152T neurons (Figure S3F) PubMed:27594586
Interestingly, this ratio is also increased, but to a lesser extent, in tau-A152T neurons (Figure S3F) PubMed:27594586
Tau-A152T displayed very similar degradation dynamics, although this mutation slightly reduced tau’s rates of lysosomal degradation (20% inhibition) when compared with WT tau (Fig. 1a,b). PubMed:29024336
For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300
For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300
For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300
Another MAPT polymorphism (A152T) was recently identified in patients diagnosed with progressive supranuclear palsy (PSP) (72–74). PubMed:29191965
Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930
Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930
Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930
In addition, this A152T tau enhances the formation of oligomers but not fibres PubMed:26631930
Some tau mutations (such as A152T and R5H) may cause loss of tau function as well (as discussed above) PubMed:26631930
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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.