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<p>Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized as a slowly progressing neurodegenerative disease marked by senile plaques and neurofibrillary tangles due to the buildup of amyloid-beta peptide (Aβ) and phosphorylated tau in the brain. It is reported that arctigenin (ATG) reduces the level of the enzyme 1 that cleaves β-site amyloid precursor protein and increases Aβ clearance by enhancing autophagy. Compound ARC-18 is a derivative of ATG. The main objective of this study is to investigate whether ARC-18 could improve cognitive function and disease progression by promoting autophagy in Alzheimer-like animal models. Three-month-old 5 × FAD mice were orally treated with the drug for three consecutive months. Water maze and novel object recognition were used to assess cognitive abilities of 5 × FAD mice. In the hippocampus of the mice’ brain, APP processing-related proteins (sAPP<sub>β</sub>, BACE1) and autophagy-related proteins (LC3B, P62, LAMP1) were detected. N2a/APPswe cells were used to do experiments to further identify the effect and mechanisms of the drug. Our study demonstrated that ARC-18 enhances the behavioral performance of 5 × FAD mice and mitigates Aβ aggregation in the hippocampus and cortex. This effect is achieved through the activation of adiponectin receptor 1 (AdipoR1)-mediated autophagy and the reduction of Aβ production by modulating amyloid precursor protein (APP) processing. Therefore, ARC-18 holds promise as a potential therapeutic agent for Alzheimer’s disease.</p>

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ARC-18 Alleviates Alzheimer-like Pathology and Cognitive Deficits via AdipoR1-Mediated Activation of Autophagy and Modulation of APP Processing

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Shangming Li,
  • Bocheng Xiong,
  • Nan Xu,
  • Lulin Nie,
  • Kaiwu He,
  • Guiliang Zhang,
  • Chongyang Chen,
  • Zaijun Zhang,
  • Maggie Pui Man Hoi,
  • Xifei Yang

摘要

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized as a slowly progressing neurodegenerative disease marked by senile plaques and neurofibrillary tangles due to the buildup of amyloid-beta peptide (Aβ) and phosphorylated tau in the brain. It is reported that arctigenin (ATG) reduces the level of the enzyme 1 that cleaves β-site amyloid precursor protein and increases Aβ clearance by enhancing autophagy. Compound ARC-18 is a derivative of ATG. The main objective of this study is to investigate whether ARC-18 could improve cognitive function and disease progression by promoting autophagy in Alzheimer-like animal models. Three-month-old 5 × FAD mice were orally treated with the drug for three consecutive months. Water maze and novel object recognition were used to assess cognitive abilities of 5 × FAD mice. In the hippocampus of the mice’ brain, APP processing-related proteins (sAPPβ, BACE1) and autophagy-related proteins (LC3B, P62, LAMP1) were detected. N2a/APPswe cells were used to do experiments to further identify the effect and mechanisms of the drug. Our study demonstrated that ARC-18 enhances the behavioral performance of 5 × FAD mice and mitigates Aβ aggregation in the hippocampus and cortex. This effect is achieved through the activation of adiponectin receptor 1 (AdipoR1)-mediated autophagy and the reduction of Aβ production by modulating amyloid precursor protein (APP) processing. Therefore, ARC-18 holds promise as a potential therapeutic agent for Alzheimer’s disease.