Cited by 277Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAntioxidant Activity and Oxidative Stress

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Aβ and Tau Toxicities in Alzheimer's Are Linked via Oxidative Stress-Induced P38 Activation: Protective Role of Vitamin E

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Giraldo, E., Lloret, A., Fuchsberger, T., Viña, J.·2014·Redox Biology

DOI 10.1016/j.redox.2014.03.002PMC PMC4099506

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Abstract

Oxidative stress is a hallmark of Alzheimer's disease (AD). We propose that rather than causing damage because of the action of free radicals, oxidative stress deranges signaling pathways leading to tau hyperphosphorylation, a hallmark of the disease. Indeed, incubation of neurons in culture with 5 µM beta-amyloid peptide (Aβ) causes an activation of p38 MAPK (p38) that leads to tau hyperphosphorylation. Inhibition of p38 prevents Aβ-induced tau phosphorylation. Aβ-induced effects are prevented when neurons are co-incubated with trolox (the water-soluble analog of vitamin E). We have confirmed these results in vivo, in APP/PS1 double transgenic mice of AD. We have found that APP/PS1 transgenic mice exhibit a high level of P-p38 in the hippocampus but not in cortex and this is prevented by feeding animals with a diet supplemented with vitamin E. Our results underpin the role of oxidative stress in the altered cell signaling in AD pathology and suggest that antioxidant prevention may be useful in AD therapeutics.

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Background

Authors: Giraldo, E., Lloret, A., Fuchsberger, T., & Viña, J.
Affiliations: Universitat de València (ES)
Corresponding author: Viña, J.
ORCID: Giraldo, E.
Lloret, A.
Fuchsberger, T.
Viña, J.
Venue: Redox Biology
Publisher: Elsevier BV
Published: 2014
Volume: 2
Pages: 873-877
ISSN: 2213-2317 (ISSN-L)
DOI: 10.1016/j.redox.2014.03.002
PMC: PMC4099506
OpenAlex: W2039173359
Cited by: 268
References: 28
Citations by year: 2026: 10 · 2025: 18 · 2024: 23 · 2023: 34 · 2022: 27 · 2021: 26 · 2020: 27 · 2019: 24 · 2018: 22 · 2017: 21 · 2016: 12 · 2015: 19 · 2014: 3
FWCI: 12.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 68 d)
Locations: Redox Biology (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Spanish Ministry of Education and Science (MEC) (SAF2010-19498)
“Red Tematica de investigacion cooperativa en envejecimiento y fragilidad” (RETICEF) (ISCIII2006-RED13-027, ISCIII2012-RED-43-029)
“Conselleria d’Educació, Cultura i Esport de la Generalitat Valenciana” (PROMETEO2010/074)
“Fundació Gent Per Gent de la Comunitat Valenciana” (35NEURO)
INCLIVA (RS2012-609)
EU (CM1001, FRAILOMIC-HEALTH.2012.2.1.1-2)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: Alzheimer's disease, amyloid-beta, tau hyperphosphorylation, oxidative stress, p38 MAPK, vitamin E, Trolox, APP/PS1 mice, hippocampus, antioxidant therapy, neuronal signaling
MeSH terms: Alzheimer Disease, Animals, Cells, Cultured, Disease Models, Animal, Hippocampus, Male, Mice, Transgenic, Neurons, Phosphorylation, Vitamin E, Amyloid beta-Peptides, tau Proteins, Oxidative Stress, Protective Agents, p38 Mitogen-Activated Protein Kinases, Mice, Rats

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Aβ and Tau Toxicities in Alzheimer's Are Linked via Oxidative Stress-Induced P38 Activation: Protective Role of Vitamin E

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