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Article

Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease

by
Marilena M. Bourdakou
,
Eleni M. Loizidou
and
George M. Spyrou
*
Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(8), 952; https://doi.org/10.3390/antiox14080952 (registering DOI)
Submission received: 7 July 2025 / Revised: 29 July 2025 / Accepted: 30 July 2025 / Published: 2 August 2025

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD.
Keywords: Alzheimer’s disease; extra virgin olive oil; NRF2; NFE2L2; interactome; regulome Alzheimer’s disease; extra virgin olive oil; NRF2; NFE2L2; interactome; regulome

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MDPI and ACS Style

Bourdakou, M.M.; Loizidou, E.M.; Spyrou, G.M. Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease. Antioxidants 2025, 14, 952. https://doi.org/10.3390/antiox14080952

AMA Style

Bourdakou MM, Loizidou EM, Spyrou GM. Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease. Antioxidants. 2025; 14(8):952. https://doi.org/10.3390/antiox14080952

Chicago/Turabian Style

Bourdakou, Marilena M., Eleni M. Loizidou, and George M. Spyrou. 2025. "Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease" Antioxidants 14, no. 8: 952. https://doi.org/10.3390/antiox14080952

APA Style

Bourdakou, M. M., Loizidou, E. M., & Spyrou, G. M. (2025). Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease. Antioxidants, 14(8), 952. https://doi.org/10.3390/antiox14080952

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