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<p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder leading to dementia. This study investigated the effects of catalpol and tetramethylpyrazine (CT) on AD. AD mice were treated with CT, TGN020, 6RK73, and Stattic. The Morris water maze task was employed to assess spatial learning and memory. Histological staining was used to evaluate hippocampal neuronal damage, Aβ1-40 clearance, and AQP4 protein distribution in the hippocampus. An AD cell model was established by inducing Aβ1-42 in mouse astrocytes, followed by CT, 6RK73, and Stattic treatments. UCHL1 siRNA was transfected into astrocytes, and ubiquitination analysis was conducted. Gene expression was assessed via qRT-PCR and Western blot. CT improved spatial learning and memory in AD mice, mitigated hippocampal neuronal damage, enhanced Aβ1-40 clearance, increased UCHL1 and p-STAT3/STAT3 expression, and promoted AQP4 protein expression and its polarized distribution in the hippocampus. The improvement in spatial learning, memory, and hippocampal neuronal damage was diminished by TGN020. 6RK73 inhibited CT-induced AQP4 expression and its polarized distribution in hippocampal astrocytes. Stattic counteracted CT-induced upregulation of UCHL1 in the hippocampus. UCHL1 facilitated AQP4 deubiquitination. Silencing UCHL1 or treating with 6RK73 blocked CT-induced AQP4 expression and its polarized distribution in Aβ1-42-treated astrocytes. Stattic abolished CT-induced UCHL1 expression in Aβ1-42-treated astrocytes. CT likely promotes STAT3 phosphorylation, enhancing UCHL1 expression, which in turn facilitates AQP4 expression and its polarized distribution in hippocampal astrocytes, providing therapeutic benefits in AD. These findings suggest CT as a potential therapeutic agent for AD.</p>

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Catalpol and tetramethylpyrazine relieve Alzheimer's disease by facilitating AQP4 protein expression and polarized distribution in hippocampal astrocytes via inducing the STAT3-mediated UCHL1 expression

  • 期刊论文

  • 发表日期：

    2026年5月25日

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  • Chujun Deng,
  • Mengting Zhu,
  • Jing Yuan,
  • Tianxiang Yin,
  • Huize Chen,
  • Shengxi Meng

摘要

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder leading to dementia. This study investigated the effects of catalpol and tetramethylpyrazine (CT) on AD. AD mice were treated with CT, TGN020, 6RK73, and Stattic. The Morris water maze task was employed to assess spatial learning and memory. Histological staining was used to evaluate hippocampal neuronal damage, Aβ1-40 clearance, and AQP4 protein distribution in the hippocampus. An AD cell model was established by inducing Aβ1-42 in mouse astrocytes, followed by CT, 6RK73, and Stattic treatments. UCHL1 siRNA was transfected into astrocytes, and ubiquitination analysis was conducted. Gene expression was assessed via qRT-PCR and Western blot. CT improved spatial learning and memory in AD mice, mitigated hippocampal neuronal damage, enhanced Aβ1-40 clearance, increased UCHL1 and p-STAT3/STAT3 expression, and promoted AQP4 protein expression and its polarized distribution in the hippocampus. The improvement in spatial learning, memory, and hippocampal neuronal damage was diminished by TGN020. 6RK73 inhibited CT-induced AQP4 expression and its polarized distribution in hippocampal astrocytes. Stattic counteracted CT-induced upregulation of UCHL1 in the hippocampus. UCHL1 facilitated AQP4 deubiquitination. Silencing UCHL1 or treating with 6RK73 blocked CT-induced AQP4 expression and its polarized distribution in Aβ1-42-treated astrocytes. Stattic abolished CT-induced UCHL1 expression in Aβ1-42-treated astrocytes. CT likely promotes STAT3 phosphorylation, enhancing UCHL1 expression, which in turn facilitates AQP4 expression and its polarized distribution in hippocampal astrocytes, providing therapeutic benefits in AD. These findings suggest CT as a potential therapeutic agent for AD.