Physiological Release of Endogenous Tau is Stimulated by Neuronal Activity

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2013 Feb 16

PMID 23412472

Citations 339

Authors

Amy M Pooler

Emma C Phillips

Dawn H W Lau

Wendy Noble

Diane P Hanger

Affiliations

Soon will be listed here.

Abstract

Propagation of tau pathology is linked with progressive neurodegeneration, but the mechanism underlying trans-synaptic spread of tau is unknown. We show that stimulation of neuronal activity, or AMPA receptor activation, induces tau release from healthy, mature cortical neurons. Notably, phosphorylation of extracellular tau appears reduced in comparison with intracellular tau. We also find that AMPA-induced release of tau is calcium-dependent. Blocking pre-synaptic vesicle release by tetanus toxin and inhibiting neuronal activity with tetrodotoxin both significantly impair AMPA-mediated tau release. Tau secretion is therefore a regulatable process, dysregulation of which could lead to the spread of tau pathology in disease.

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