Resveratrol improves Aβ1-42 Alzheimer's cognitive impairment by activating AMPK/ULK1 and SIRT1/NF-κB autophagy.

Aging is a primary risk factor for Alzheimer's disease (AD), a devastating neurodegenerative disorder characterized by progressive cognitive decline. Current therapies primarily manage symptoms, leaving a critical need for disease-modifying strategies. Targeting cellular senescence, a state of irreversible cell cycle arrest implicated in neurodegeneration, offers a promising therapeutic avenue. Resveratrol (RV), a natural polyphenolic compound, is known for its anti-aging properties, often linked to its modulation of autophagy and oxidative stress. However, its precise mechanisms in the context of AD pathology, particularly involving senescence and specific signaling pathways, remain incompletely understood.

Researchers investigated Resveratrol's effects and mechanisms in an Aβ1-42-induced AD model. In vivo, mice were administered Resveratrol (specific dose not detailed in abstract) to assess its impact on aging-related markers and autophagy pathways. In vitro, cell models were treated with Resveratrol to evaluate its ability to mitigate Aβ1-42-induced cell viability loss and excessive reactive oxygen species (ROS) production. Mechanistic analyses focused on identifying specific signaling pathways involved in Resveratrol-induced autophagy activation, utilizing techniques to probe AMPK/ULK1 and SIRT1/NF-κB pathway activity.

In the Aβ1-42-induced AD model mice, Resveratrol administration significantly reduced the expression of aging-related markers, indicating a delay in cellular senescence. This was accompanied by the activation of autophagy-associated signaling pathways. In vitro, Resveratrol treatment markedly attenuated Aβ1-42-induced cell viability loss and significantly reduced excessive reactive oxygen species (ROS) production. These findings suggest a direct protective effect at the cellular level against amyloid-beta toxicity. Further mechanistic analyses elucidated that Resveratrol-induced autophagy activation was intricately linked to the AMP-activated protein kinase/UNC-51-like kinase 1 (AMPK/ULK1) pathway. Additionally, the silent information regulator 1/nuclear factor-kappaB (SIRT1/NF-κB) pathway was found to be closely associated with Resveratrol's autophagy-promoting effects. These dual pathway activations highlight a comprehensive molecular mechanism. > Resveratrol alleviates AD-related pathological processes by promoting autophagy and delaying cellular senescence, suggesting its potential as a therapeutic agent.