PubMed 29024336

In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this agerelated disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk-associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway

BEL
p(MGI:Mapt, var("p.Pro301Leu")) decreases deg(p(MGI:Mapt))
Hash
aab72cc1f0
Confidence
High
MeSHAnatomy
Brain, Neurons
Networks

PubMed 29024336

An increase in overall tau levels has been observed in brains from patients bearing either P301L or A152T mutation on tau (Torres et al., 1998)

BEL
p(MGI:Mapt, var("p.Pro301Leu")) increases p(MGI:Mapt)
Hash
a6d28a44e0
Confidence
High
MeSHAnatomy
Brain
Networks

PubMed 29024336

In contrast, the P301L mutation severely impaired lysosomal uptake of tau by CMA, resulting in a sixfold decrease in degradation when compared to WT tau protein (Fig. 1c,d)

BEL
p(MGI:Mapt, var("p.Pro301Leu")) decreases deg(p(MGI:Mapt))
Hash
4b70e4ec4f
CellStructure
Lysosomes
Confidence
High
MeSHAnatomy
Brain
Networks

PubMed 29024336

Taken together, our in vitro and cell-based studies argue that these two point mutations, A152T and P301L, reduce the normal degradation of tau by CMA, although the P301L mutation has a more pronounced inhibitory effect

BEL
p(MGI:Mapt, var("p.Pro301Leu")) decreases deg(p(MGI:Mapt))
Hash
7bc1f78fe6
CellStructure
Lysosomes
Confidence
High
MeSHAnatomy
Brain
Networks

PubMed 29024336

In summary, when comparing the pathogenic tau mutation P301L with the risk-associated mutation A152T, we found that both reduced normal turnover of tau by autophagy, but that the effect of the P301L mutation was more pronounced (summarized in Fig. 2g and Fig. S6, Supporting information)

BEL
p(MGI:Mapt, var("p.Pro301Leu")) decreases deg(p(MGI:Mapt))
Hash
d798e4170a
CellStructure
Multivesicular Bodies
Confidence
High
MeSHAnatomy
Brain
Networks

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.