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Publication - Dr Daniel Whitcomb

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

    Citation

    Yi, JH, Brown, C, Whitehead, G, Piers, T, Lee, YS, Perez, CM, Regan, P, Whitcomb, DJ & Cho, K, 2017, ‘Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus’. Pharmacological Research., pp. 42-51

    Abstract

    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.

    Full details in the University publications repository