Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential

Numerous hypotheses have been proposed to explain the origin of Alzheimer’s disease (AD), a chronic neurodegenerative disorder that currently has no curative treatment. These hypotheses include the abnormal accumulation of β-amyloid and hyperphosphorylated Tau, degeneration of cholinergic neurons associated with chronic neuroinflammation and oxidative stress, and dysregulation of lipid and carbohydrate metabolism. oleanolic acid (OA), a pentacyclic triterpenoid widely distributed across plant species, has demonstrated anti-inflammatory and antioxidant activities, anti-aggregation properties, together with regulatory effects on carbohydrate and lipid metabolism. Given the diversity of hypotheses proposed for AD and its multifactorial nature, the pleiotropic actions of OA positions it as a promising candidate for preventive and therapeutic strategies. This review compiles evidence on OA and selected synthetic derivatives, analyzing their impact across the major mechanistic hypotheses of AD pathogenesis. Collectively, these findings support OA as a promising candidate to address protein aggregation, metabolic imbalance, and neuroinflammation in AD.

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Journal
Applied Sciences
Published
2026-01-04
DOI
https://doi.org/10.3390/app16010494
Primary Topic
Natural product bioactivities and synthesis
Type
article
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article

Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential

Juan Manuel Espinosa-Cabello, González Jiménez Emilio, José María Castellano, Ángel Fernández-Aparicio et al.
Applied Sciences
Natural product bioactivities and synthesis
article

Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential

Juan Manuel Espinosa-Cabello, González Jiménez Emilio, José María Castellano, Ángel Fernández-Aparicio, Gisela Perez-Muñoz, Javier S. Perona
article en

Abstract

Numerous hypotheses have been proposed to explain the origin of Alzheimer’s disease (AD), a chronic neurodegenerative disorder that currently has no curative treatment. These hypotheses include the abnormal accumulation of β-amyloid and hyperphosphorylated Tau, degeneration of cholinergic neurons associated with chronic neuroinflammation and oxidative stress, and dysregulation of lipid and carbohydrate metabolism. oleanolic acid (OA), a pentacyclic triterpenoid widely distributed across plant species, has demonstrated anti-inflammatory and antioxidant activities, anti-aggregation properties, together with regulatory effects on carbohydrate and lipid metabolism. Given the diversity of hypotheses proposed for AD and its multifactorial nature, the pleiotropic actions of OA positions it as a promising candidate for preventive and therapeutic strategies. This review compiles evidence on OA and selected synthetic derivatives, analyzing their impact across the major mechanistic hypotheses of AD pathogenesis. Collectively, these findings support OA as a promising candidate to address protein aggregation, metabolic imbalance, and neuroinflammation in AD.

Applied SciencesVol. 16(1)
Universidad de Granada (ES), Instituto de la Grasa (ES), Instituto de Investigación Biosanitaria de Granada (ES)
Good health and well-being
Openalex Percentile: Top 97%
Natural product bioactivities and synthesis
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Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential — Juan Manuel Espinosa-Cabello, González Jiménez Emilio, et al. · Applied Sciences (2026) | TGRS Research Map | TGRS