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| Auteurs principaux: | , , , , , , , , |
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| Format: | Artículo Open Access |
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Wiley
2025
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| Accès en ligne: | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70069 |
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- Atractylenolide III Mitigates Alzheimer's Disease by Enhancing Autophagy via the YY1‐TFEB Pathway Xiaowei Zhang Shuang Chu Yanli Huang Zhonghua Li Junying Song Pan Wang Yunfang Su Zhenqiang Zhang Zhishen Xie Phytotherapy Research ABSTRACTAutophagy dysregulation serves as a significant pathogenic factor in Alzheimer's disease (AD), with transcription factor EB (TFEB) acting as a pivotal transcription factor that governs the process of autophagy. Atractylenolide III (AT‐III), a terpenoid compound found in medicinal Atractylodes macrocephala Koidz, is well‐known for its role in antioxidant and anti‐inflammatory activities. The purpose of this study is to explore the beneficial impact of AT‐III on AD pathology and identify the mechanisms involved. C. elegans CL4176, SH‐SY5Y APPSWE, and APP/PS1 mice were used to investigate the efficacy and possible mechanism of AT‐III on the treatment of AD. AT‐III reduced amyloid protein (Aβ) deposition in C. elegans CL4176 heads, prolonged the paralysis time, and reduced Aβ levels in SH‐SY5Y APPSWE cells. AT‐III improved the learning and memory ability of APP/PS1 mice and decreased the deposition of Aβ plaques. Transcriptomics and experimental validation showed that AT‐III stimulated transcription and translation of autolysosome‐associated genes. AT‐III enhanced co‐localization of LC3 and LAMP2 with Aβ in APP/PS1 mice. Meanwhile, AT‐III increased TFEB transcriptional activity, mRNA, and protein levels in the nucleus. Furthermore, AT‐III enhanced the expression of Yin Yang 1 (YY1) protein, an upstream regulator of TFEB, and led to the stimulation of autophagy and lysosome biogenesis both in vivo and in vitro. The observed effects were reversed upon silencing YY1. AT‐III may regulate the YY1‐TFEB pathway, thereby restoring autophagy flux disturbances and ameliorating AD‐related pathological changes and cognitive decline. This study provides a promising lead compound for intervention in AD. 10.1002/ptr.70069 http://onlinelibrary.wiley.com/termsAndConditions#vor