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The Importance of Tau Phosphorylation for Neurodegenerative Diseases

Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neurona...

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Autores principales: Noble, Wendy, Hanger, Diane P., Miller, Christopher C. J., Lovestone, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696910/
https://www.ncbi.nlm.nih.gov/pubmed/23847585
http://dx.doi.org/10.3389/fneur.2013.00083
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author Noble, Wendy
Hanger, Diane P.
Miller, Christopher C. J.
Lovestone, Simon
author_facet Noble, Wendy
Hanger, Diane P.
Miller, Christopher C. J.
Lovestone, Simon
author_sort Noble, Wendy
collection PubMed
description Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders.
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spelling pubmed-36969102013-07-11 The Importance of Tau Phosphorylation for Neurodegenerative Diseases Noble, Wendy Hanger, Diane P. Miller, Christopher C. J. Lovestone, Simon Front Neurol Neuroscience Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders. Frontiers Media S.A. 2013-07-01 /pmc/articles/PMC3696910/ /pubmed/23847585 http://dx.doi.org/10.3389/fneur.2013.00083 Text en Copyright © 2013 Noble, Hanger, Miller and Lovestone. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Neuroscience
Noble, Wendy
Hanger, Diane P.
Miller, Christopher C. J.
Lovestone, Simon
The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title_full The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title_fullStr The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title_full_unstemmed The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title_short The Importance of Tau Phosphorylation for Neurodegenerative Diseases
title_sort importance of tau phosphorylation for neurodegenerative diseases
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696910/
https://www.ncbi.nlm.nih.gov/pubmed/23847585
http://dx.doi.org/10.3389/fneur.2013.00083
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