Work

Ginkgolide A enhances cognition and reduces amyloid-β by activating autophagy in the murine 5xFAD Alzheimer’s disease model

Year: 2025

Type: article

Abstract: BACKGROUND: Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder closely associated with impaired autophagy. Ginkgolide A (GA), a principal bioactive constituent of Ginkgo biloba, has garnered attention for its antioxidant, anti-inflammatory, and autophagy-modulating properties. MAIN TEXT: To evaluate the therapeutic potential of GA, we administered oral GA (20 mg/kg/day) for four weeks to 5xFAD transgenic mice. GA treatment significantly reduced soluble and insoluble forms of amyloid-β (Aβ) in the cortex and hippocampus, and markedly decreased Aβ plaque deposition. Cognitive performance was improved, as evidenced by increased spontaneous alternation in the Y-maze test. GA enhanced synaptic plasticity, indicated by increased expression of the synaptic markers synaptophysin 11 (SP11) and postsynaptic density 95 (PSD95). At the molecular level, GA activated autophagy by modulating PI3K-Akt signaling, relieving endoplasmic reticulum (ER) stress, and enhancing energy stress responses, ultimately leading to mTOR pathway suppression. CONCLUSION: These findings demonstrate that GA is a promising multifunctional therapeutic candidate for AD. Its ability to regulate autophagy and related signaling pathways provides new insights into disease mitigation and cognitive improvement.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118472

Authors: Subin Park, Miey Park, Hae-Jeung Lee

Institution: Gachon University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,610