Scholarlink

<p>Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by pathological protein aggregation and oxidative stress, leading to progressive neurodegeneration. Enhancing autophagy, the primary intracellular pathway for clearing misfolded proteins, represents a promising therapeutic strategy. In this study, we identify Araloside A (ARA), a triterpenoid saponin derived from <i>Aralia elata</i>, as a potent autophagy inducer that alleviates AD- and PD-related pathology. In neuronal cell models, ARA promotes autophagosome formation, increases LC3-II and Beclin-1 levels, and decreases P62, indicating enhanced autophagic activity. Mechanistic investigations reveal that ARA directly binds to Raf, MEK, and ERK proteins and activates autophagy in a Raf/MEK/ERK-dependent manner. This activation facilitates the clearance of APP, total Tau, phosphorylated Tau, and α-synuclein, thereby reducing cytotoxicity. Furthermore, in transgenic <i>Caenorhabditis elegans</i> models of AD and PD, ARA treatment alleviates protein aggregation and behavioral deficits via ERK-dependent autophagy. Together, these findings identify ARA as a natural compound that enhances autophagic clearance of neurotoxic aggregates via Raf/MEK/ERK pathway activation, offering promising therapeutic insights for neurodegenerative proteinopathies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Araloside A Induces Raf/MEK/ERK-Dependent Autophagy to Mitigate Alzheimer’s and Parkinson’s Pathology in Cellular and C. elegans Models

  • 期刊论文

  • 发表日期：

    2025年7月31日

查看全文
  • Xue Chen,
  • Xing-Yue Zhou,
  • Cai Lan,
  • Hai-Jun Fu,
  • Zhi-Chao Li,
  • Meng-Yi Chen,
  • Yong-Ping Wen,
  • Lu Yu,
  • Da-Lian Qin,
  • An-Guo Wu,
  • Jian-Ming Wu,
  • Xiao-Gang Zhou

摘要

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by pathological protein aggregation and oxidative stress, leading to progressive neurodegeneration. Enhancing autophagy, the primary intracellular pathway for clearing misfolded proteins, represents a promising therapeutic strategy. In this study, we identify Araloside A (ARA), a triterpenoid saponin derived from Aralia elata, as a potent autophagy inducer that alleviates AD- and PD-related pathology. In neuronal cell models, ARA promotes autophagosome formation, increases LC3-II and Beclin-1 levels, and decreases P62, indicating enhanced autophagic activity. Mechanistic investigations reveal that ARA directly binds to Raf, MEK, and ERK proteins and activates autophagy in a Raf/MEK/ERK-dependent manner. This activation facilitates the clearance of APP, total Tau, phosphorylated Tau, and α-synuclein, thereby reducing cytotoxicity. Furthermore, in transgenic Caenorhabditis elegans models of AD and PD, ARA treatment alleviates protein aggregation and behavioral deficits via ERK-dependent autophagy. Together, these findings identify ARA as a natural compound that enhances autophagic clearance of neurotoxic aggregates via Raf/MEK/ERK pathway activation, offering promising therapeutic insights for neurodegenerative proteinopathies.