Tau Phosphorylation by GSK3 in Different Conditions

Ávila, Jesús; León‐Espinosa, Gonzalo; García, Elena; García-Escudero, Vega; Hernández, Félix; DeFelipe, Javier

doi:10.1155/2012/578373

Cited by 80 publications

(75 citation statements)

References 83 publications

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“…More than 30 kinases have been described as regulating Tau phosphorylation in vitro, while only a few have been confirmed in vivo. Among them, GSK3-β is an important kinase which phosphorylates Tau on more than 30 sites and seems to play a pivotal role in AD and NFT development [99]. All serine/threonine phosphatases in the brain are prone to dephosphorylate Tau in vitro except PP2C [100-104], with PP2A contributing to 71% of the phosphatase activity on Tau [105].…”

Section: Overview On Tau and Tauopathiesmentioning

confidence: 99%

“…Similarly, the deletion of IRS - 2 causes inhibition of the PI3K/Akt pathway and therefore induces Tau hyperphosphorylation [188]. Overall, the pathological effect of brain insulin resistance on Tau has mostly been attributable to the modulation of several downstream pathways [183], involving some Tau kinases (GSK-3β, JNK, ERK, and AMPK) and Tau phosphatases (PP2A and PP1), known to play a pivotal role in the development of Tau pathology [99, 191-203]. Therefore, the chronic insulin signalling impairment seen in the brains of patients with AD and tauopathies is prone to favour the development of Tau pathology through the disruption of the balance between Tau kinases and phosphatases.…”

Section: Brain Insulin Resistance In Ad and Tauopathies: Cause Or Conmentioning

confidence: 99%

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Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

et al. 2018

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Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

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Section: Overview On Tau and Tauopathiesmentioning

confidence: 99%

Section: Brain Insulin Resistance In Ad and Tauopathies: Cause Or Conmentioning

confidence: 99%

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

et al. 2018

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“…Although the aggregation of HP tau species has been proposed to represent a compensatory neuronal response against oxidative stress and to serve at least initially as a protector against cell death [79,80], the detrimental effects of abnormal tau in AD, related tautopathies and under experimental conditions are not subject to controversy [55,78,[81][82][83][84].…”

Section: Alzheimer's and Parkinson's Diseases And Air Pollutionmentioning

confidence: 99%

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

et al. 2016

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Air pollution (indoor and outdoor air) is a major issue in public health as epidemiological studies haven pointed to the numerous detrimental health consequences (notably, respiratory and cardiovascular pathology). In the last fifteen years, air pollution has also been considered as a potent environmental risk factor for neurological diseases and neuropathology. In this review, the authors examine the impact of air pollution on children's brain development and its clinical, cognitive, brain structural and metabolic consequences. Long-term potential consequences for adults' brain and effects on multiple sclerosis are also discussed. One challenge is assessing lifetime exposures to outdoor and indoor environments, including occupational exposures: how much, for how long and what type. The diffuse neuroinflammation, the damage to the neurovascular unit, and the production of auto-antibodies to neural and tight junction proteins are worrisome findings in children chronically exposed to concentrations above current standards for ozone and fine particulate matter (PM 2.5 ) and may constitute significant risk factors for the development of Article Outline

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“…Tau phosphorylation could be protective (e.g., hibernation) or toxic (e.g., hyperphosphorylation and aggregation of tau) [109]. Hyperphosphorylated tau in epitopes characteristic of AD has been identified by immunohistochemistry in 62.5% of APOE 4 and 33% of APOE 3 young MCMA carriers [30].…”

Section: Compensatory Responses Versus Neurotoxic and Neurodegenermentioning

confidence: 99%

Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

Calderón‐Garcidueñas

Franco-Lira

Mora-Tiscareño

et al. 2013

BioMed Research International

106

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Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

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Tau Phosphorylation by GSK3 in Different Conditions

Cited by 80 publications

References 83 publications

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

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