Physiological release of endogenous tau is stimulated by neuronal activity
By A. Pooler, Emma C. Phillips, Dawn H. W. Lau, Wendy Noble, D. Hanger. EMBO Reports, 2013
627 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience
View Paper: https://www.semanticscholar.org/paper/a2266fcbbf5d2b5122a419d5dc1e2ce324e9fa21
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In Cellular and Molecular Neuroscience
In Cognitive Neuroscience
Citations in the corpus
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “As expected, increased neuronal activity is shown to promote both physiological and pathological release of tau in vitro, and exacerbates tau pathology in vivo [257, 258].”
- The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans (2019, background): “This release is increased by excitatory neuronal activity (8, 9).”