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Physiological release of endogenous tau is stimulated by neuronal activity.


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.

SUBMITTER: Pooler AM 

PROVIDER: S-EPMC3615658 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Physiological release of endogenous tau is stimulated by neuronal activity.

Pooler Amy M AM   Phillips Emma C EC   Lau Dawn H W DH   Noble Wendy W   Hanger Diane P DP  

EMBO reports 20130215 4


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 tox  ...[more]

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