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Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration

There is an emerging link between the accumulation of iron in the brain and abnormal tau pathology in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). Studies have demonstrated that iron can regulate tau phosphorylation by inducing the activity of multiple kinases that prom...

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Autores principales: Rao, Shalini S., Adlard, Paul Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108061/
https://www.ncbi.nlm.nih.gov/pubmed/30174587
http://dx.doi.org/10.3389/fnmol.2018.00276
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author Rao, Shalini S.
Adlard, Paul Anthony
author_facet Rao, Shalini S.
Adlard, Paul Anthony
author_sort Rao, Shalini S.
collection PubMed
description There is an emerging link between the accumulation of iron in the brain and abnormal tau pathology in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). Studies have demonstrated that iron can regulate tau phosphorylation by inducing the activity of multiple kinases that promote tau hyperphosphorylation and potentially also by impacting protein phosphatase 2A activity. Iron is also reported to induce the aggregation of hyperphosphorylated tau, possibly through a direct interaction via a putative iron binding motif in the tau protein, facilitating the formation of neurofibrillary tangles (NFTs). Furthermore, in human studies high levels of iron have been reported to co-localize with tau in NFT-bearing neurons. These data, together with our own work showing that tau has a role in mediating cellular iron efflux, provide evidence supporting a critical tau:iron interaction that may impact both the symptomatic presentation and the progression of disease. Importantly, this may also have relevance for therapeutic directions, and indeed, the use of iron chelators such as deferiprone and deferoxamine have been reported to alleviate the phenotypes, reduce phosphorylated tau levels and stabilize iron regulation in various animal models. As these compounds are also moving towards clinical translation, then it is imperative that we understand the intersection between iron and tau in neurodegeneration. In this article, we provide an overview of the key pathological and biochemical interactions between tau and iron. We also review the role of iron and tau in disease pathology and the potential of metal-based therapies for tauopathies.
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spelling pubmed-61080612018-08-31 Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration Rao, Shalini S. Adlard, Paul Anthony Front Mol Neurosci Neuroscience There is an emerging link between the accumulation of iron in the brain and abnormal tau pathology in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). Studies have demonstrated that iron can regulate tau phosphorylation by inducing the activity of multiple kinases that promote tau hyperphosphorylation and potentially also by impacting protein phosphatase 2A activity. Iron is also reported to induce the aggregation of hyperphosphorylated tau, possibly through a direct interaction via a putative iron binding motif in the tau protein, facilitating the formation of neurofibrillary tangles (NFTs). Furthermore, in human studies high levels of iron have been reported to co-localize with tau in NFT-bearing neurons. These data, together with our own work showing that tau has a role in mediating cellular iron efflux, provide evidence supporting a critical tau:iron interaction that may impact both the symptomatic presentation and the progression of disease. Importantly, this may also have relevance for therapeutic directions, and indeed, the use of iron chelators such as deferiprone and deferoxamine have been reported to alleviate the phenotypes, reduce phosphorylated tau levels and stabilize iron regulation in various animal models. As these compounds are also moving towards clinical translation, then it is imperative that we understand the intersection between iron and tau in neurodegeneration. In this article, we provide an overview of the key pathological and biochemical interactions between tau and iron. We also review the role of iron and tau in disease pathology and the potential of metal-based therapies for tauopathies. Frontiers Media S.A. 2018-08-17 /pmc/articles/PMC6108061/ /pubmed/30174587 http://dx.doi.org/10.3389/fnmol.2018.00276 Text en Copyright © 2018 Rao and Adlard. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Rao, Shalini S.
Adlard, Paul Anthony
Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title_full Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title_fullStr Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title_full_unstemmed Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title_short Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
title_sort untangling tau and iron: exploring the interaction between iron and tau in neurodegeneration
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108061/
https://www.ncbi.nlm.nih.gov/pubmed/30174587
http://dx.doi.org/10.3389/fnmol.2018.00276
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