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.
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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.
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