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Synaptic Localisation of Tau. | LitMetric

Synaptic Localisation of Tau.

Adv Exp Med Biol

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Published: April 2020

AI Article Synopsis

  • Tau protein, associated with microtubules, accumulates abnormally in neurons during Alzheimer's and other tauopathies, leading to neuronal death and cognitive decline.
  • Highly phosphorylated and acetylated tau can disrupt synaptic function by mislocalizing at synapses, which harms synaptic vesicle release and overall neuronal activity.
  • Understanding tau's different roles and locations within neurons is crucial for uncovering mechanisms of tauopathies and could aid in developing potential therapies.

Article Abstract

The microtubule-associated protein tau has been identified in several intraneuronal compartments, including in association with synapses. In Alzheimer's disease, frontotemporal dementia and related tauopathies, highly phosphorylated tau accumulates as intraneuronal protein aggregates that are likely responsible for the demise of neurons and the subsequent progressive cognitive decline. However, the molecular mechanisms underlying such tau-mediated damage in the tauopathies is not fully understood. Tauopathy induces loss of synapses, which is one of the earliest structural correlates of cognitive dysfunction and disease progression. Notably, altered post-translational modifications of tau, including increased phosphorylation and acetylation, augment the mislocalisation of tau to synapses, impair synaptic vesicle release and might influence the activity-dependent release of tau from neurons. Thus, disease-associated accumulation of modified tau at the synapse adversely affects critical neuronal processes that are linked to neuronal activity and synaptic function. These findings emphasise the importance of gaining a comprehensive understanding of the diverse roles of tau at distinct intraneuronal locations. An improved knowledge of the impact of synaptic tau under physiological and pathological conditions and how tau localisation impacts on neuronal function will provide valuable insights that may lead to the development of new therapies for the tauopathies.

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Source
http://dx.doi.org/10.1007/978-981-32-9358-8_9DOI Listing

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