Unfolded protein response activates glycogen synthase kinase-3 via selective lysosomal degradation

D.A.T. Nijholt, A. Nolle, E.S. van Haastert, H. Edelijn, R.F.G. Toonen, J.J.M. Hoozemans, W. Scheper

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The unfolded protein response (UPR) is a stress response that is activated upon disturbed homeostasis in the endoplasmic reticulum. In Alzheimer's disease, as well as in other tauopathies, the UPR is activated in neurons that contain early tau pathology. A recent genome-wide association study identified genetic variation in a UPR transducer as a risk factor for tauopathy, supporting a functional connection between UPR activation and tau pathology. Here we show that UPR activation increases the activity of the major tau kinase glycogen synthase kinase (GSK)-3 in vitro via a selective removal of inactive GSK-3 phosphorylated at Ser
Original languageEnglish
Pages (from-to)1759-1771
JournalNeurobiology of Aging
Volume34
Issue number7
DOIs
Publication statusPublished - 2013

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