Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies?
Hyperphosphorylation and aggregation of the microtubule-associated protein tau in brain, are pathological hallmarks of a large family of neurodegenerative disorders, named tauopathies, which include Alzheimer’s disease. It has been shown that increased phosphorylation of tau destabilizes tau-microtu...
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Online Access: | http://dx.doi.org/10.1155/2015/151979 |
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doaj-f2c5a59f82e948a28a8c1b9f67c5afc82020-11-25T01:17:21ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942015-01-01201510.1155/2015/151979151979Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies?Seyedeh Maryam Alavi Naini0Nadia Soussi-Yanicostas1INSERM UMR 1141, Hôpital Robert Debré, Paris, FranceINSERM UMR 1141, Hôpital Robert Debré, Paris, FranceHyperphosphorylation and aggregation of the microtubule-associated protein tau in brain, are pathological hallmarks of a large family of neurodegenerative disorders, named tauopathies, which include Alzheimer’s disease. It has been shown that increased phosphorylation of tau destabilizes tau-microtubule interactions, leading to microtubule instability, transport defects along microtubules, and ultimately neuronal death. However, although mutations of the MAPT gene have been detected in familial early-onset tauopathies, causative events in the more frequent sporadic late-onset forms and relationships between tau hyperphosphorylation and neurodegeneration remain largely elusive. Oxidative stress is a further pathological hallmark of tauopathies, but its precise role in the disease process is poorly understood. Another open question is the source of reactive oxygen species, which induce oxidative stress in brain neurons. Mitochondria have been classically viewed as a major source for oxidative stress, but microglial cells were recently identified as reactive oxygen species producers in tauopathies. Here we review the complex relationships between tau pathology and oxidative stress, placing emphasis on (i) tau protein function, (ii) origin and consequences of reactive oxygen species production, and (iii) links between tau phosphorylation and oxidative stress. Further, we go on to discuss the hypothesis that tau hyperphosphorylation and oxidative stress are two key components of a vicious circle, crucial in neurodegenerative tauopathies.http://dx.doi.org/10.1155/2015/151979 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seyedeh Maryam Alavi Naini Nadia Soussi-Yanicostas |
spellingShingle |
Seyedeh Maryam Alavi Naini Nadia Soussi-Yanicostas Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? Oxidative Medicine and Cellular Longevity |
author_facet |
Seyedeh Maryam Alavi Naini Nadia Soussi-Yanicostas |
author_sort |
Seyedeh Maryam Alavi Naini |
title |
Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? |
title_short |
Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? |
title_full |
Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? |
title_fullStr |
Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? |
title_full_unstemmed |
Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies? |
title_sort |
tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2015-01-01 |
description |
Hyperphosphorylation and aggregation of the microtubule-associated protein tau in brain, are pathological hallmarks of a large family of neurodegenerative disorders, named tauopathies, which include Alzheimer’s disease. It has been shown that increased phosphorylation of tau destabilizes tau-microtubule interactions, leading to microtubule instability, transport defects along microtubules, and ultimately neuronal death. However, although mutations of the MAPT gene have been detected in familial early-onset tauopathies, causative events in the more frequent sporadic late-onset forms and relationships between tau hyperphosphorylation and neurodegeneration remain largely elusive. Oxidative stress is a further pathological hallmark of tauopathies, but its precise role in the disease process is poorly understood. Another open question is the source of reactive oxygen species, which induce oxidative stress in brain neurons. Mitochondria have been classically viewed as a major source for oxidative stress, but microglial cells were recently identified as reactive oxygen species producers in tauopathies. Here we review the complex relationships between tau pathology and oxidative stress, placing emphasis on (i) tau protein function, (ii) origin and consequences of reactive oxygen species production, and (iii) links between tau phosphorylation and oxidative stress. Further, we go on to discuss the hypothesis that tau hyperphosphorylation and oxidative stress are two key components of a vicious circle, crucial in neurodegenerative tauopathies. |
url |
http://dx.doi.org/10.1155/2015/151979 |
work_keys_str_mv |
AT seyedehmaryamalavinaini tauhyperphosphorylationandoxidativestressacriticalviciouscircleinneurodegenerativetauopathies AT nadiasoussiyanicostas tauhyperphosphorylationandoxidativestressacriticalviciouscircleinneurodegenerativetauopathies |
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1725146316475990016 |