Artemisinin Activates AMPK to Rescue Neuronal Cells and 3xTg Mice from Aβ1-42 Neurotoxicity.

作者：Yi-Tian Chen, Wen-Jun Xiong, Li-Jun Ge, Wen-Hua Zheng · 发表于：Current Neuropharmacology · 年份：2026 · DOI：10.2174/011570159x504863260824051801 · 研究领域：Medicine

INTRODUCTION Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a multifactorial etiology, including amyloid β1-42 (Aβ1-42) accumulation, oxidative stress, tau hyperphosphorylation, and neuroinflammation. Among these pathological processes, redox imbalance and inflammation are key drivers of neuronal injury and are closely linked to dysregulation of AMPK signaling. Artemisinin (ART), a clinically safe antimalarial sesquiterpene lactone, has emerged as a promising neuroprotective candidate due to its antioxidant and anti-inflammatory properties. However, its role in modulating AMP-activated protein kinase (AMPK)-dependent neuroprotection in AD remains to be fully elucidated. Given that AMPK is a master regulator of cellular energy homeostasis, oxidative stress mitigation, and neuronal survival, and that its progressive dysregulation heavily accelerates Alzheimer's disease pathology, this study aimed to determine whether artemisinin (ART) counteracts Aβ1-42-induced neurotoxicity through the targeted activation of AMPK signaling. This work provides critical mechanistic insights supporting the therapeutic repurposing of ART for AD intervention. METHODS Therefore, Aβ1-42-insulted PC12 catecholaminergic, SH-SY5Y neuroblastoma, and primary neuronal cell cultures were used to assess the neuroprotective effects of ART. Compound C and shAMPK were used to confirm AMPK dependency. In vivo efficacy was assessed with 3xTg-AD mice. RESULTS ART restored...