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Synaptic Localisation of Tau.

Diane P Hanger1, Despoina Goniotaki2, Wendy Noble2

  • 1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. diane.hanger@kcl.ac.uk.

Advances in Experimental Medicine and Biology
|February 26, 2020
PubMed
Summary

Altered tau protein in brain synapses contributes to neuronal damage and cognitive decline in tauopathies like Alzheimer's disease. Understanding synaptic tau's role is key to developing new treatments.

Keywords:
Tau; Synapse; Dementia; Tauopathy; Frontotemporal dementia; Alzheimer’s disease; Neuronal activity; Phosphorylation; Acetylation, Tau release

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Microtubule-associated protein tau is found in neurons, including synapses.
  • In tauopathies, abnormal tau aggregates cause neuronal death and cognitive decline.
  • Synaptic loss is an early sign of cognitive dysfunction in tauopathies.

Purpose of the Study:

  • To investigate the molecular mechanisms of tau-mediated neuronal damage in tauopathies.
  • To understand the role of tau modifications and localization at synapses.
  • To explore how synaptic tau impacts neuronal function and disease progression.

Main Methods:

  • Analysis of tau protein localization within neurons.
  • Investigation of post-translational modifications of tau (phosphorylation, acetylation).
  • Assessment of tau's impact on synaptic vesicle release and neuronal activity.

Main Results:

  • Altered tau modifications (e.g., phosphorylation, acetylation) lead to tau mislocalization at synapses.
  • Modified synaptic tau impairs synaptic vesicle release and neuronal function.
  • Disease-associated tau accumulation at synapses negatively affects neuronal processes.

Conclusions:

  • Synaptic tau plays a critical role in neuronal dysfunction and cognitive decline in tauopathies.
  • Understanding tau's diverse roles at different neuronal locations is crucial.
  • Targeting synaptic tau may offer new therapeutic strategies for tauopathies.