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Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus

Yi, JH; Brown, C; Whitehead, G; Piers, T; Lee, YS; Perez, CM; Regan, P; ... Cho, K; + view all (2017) Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus. Pharmacological Research , 121 pp. 42-51. 10.1016/j.phrs.2017.04.015. Green open access

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Abstract

Evidence suggests that the stress hormones glucocorticoids (GCs) can cause cognitive deficits and neurodegeneration. Previous studies have found GCs facilitate physiological synapse weakening, termed long-term depression (LTD), though the precise mechanisms underlying this are poorly understood. Here we show that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse weakening signals. Critically, this ultimately leads to phosphorylation of the microtubule associated protein tau, specifically at the serine 396 residue, and this is a causal factor in the GC-mediated impairment of synaptic function. These findings reveal the link between GCs and synapse weakening signals, and the potential for stress-induced priming of neurodegeneration. This could have important implications for our understanding of how stress can lead to neurodegenerative disease.

Type: Article
Title: Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.phrs.2017.04.015
Publisher version: https://doi.org/10.1016/j.phrs.2017.04.015
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: GSK-3, Glucocorticoids, Long-term potentiation, Tau
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10075841
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