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Comment
. 2013 Sep 4;33(36):14285-7.
doi: 10.1523/JNEUROSCI.2961-13.2013.

Tau pathology as a cause and consequence of the UPR

Brian J Stoveken  1
Affiliations
Comment

Tau pathology as a cause and consequence of the UPR

Brian J Stoveken. J Neurosci. .
No abstract available

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Figures

Figure 1.
Figure 1.
A hypothetical model of tauopathy promoted by ER stress in response to multiple stimuli. Activation of the UPR may result from toxic soluble tau species impairing ERAD through interactions with Hrd1 and VCP/p97, or directly via amyloid-β toxicity. Impaired ERAD increases unfolded protein levels in the ER lumen, triggering the UPR by competitively titrating BiP from PERK. Subsequent PERK dimerization and autophosphorylation initiates UPR signaling. The UPR may then direct the misprocessing of tau via selective GSK-3 activation, facilitating tau aggregation. Unresolved UPR activity may alternatively result in cell death via apoptosis. Aβ: Amyloid-β, UPR: Unfolded Protein Response, GSK-3: Glycogen Synthase kinase 3, p: Phosphate group, U: Ubiquitin.
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