The isoquinoline alkaloid dauricine targets multiple molecular pathways to ameliorate Alzheimer-like pathological changes in vitro

Pan Liu, Xiao Chen, Haizhe Zhou, Liqun Wang, Zaijun Zhang, Xiaohu Ren, Feiqi Zhu, Yi Guo, Xinfeng Huang, Jianjun Liu, Peter S. Spencer, Xifei Yang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Alzheimer's disease (AD), the most common neurodegenerative disease, has no effective treatment. Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, reportedly has neuroprotective effects in cerebral ischemia. Here, we investigated the effects of DAU on N2a cells stably transfected with Swedish mutant amyloid precursor protein (N2a/APP), an AD-like cell model. ELISA and Western blot analysis revealed that DAU inhibited APP processing and reduced Aβ accumulation. In addition, DAU ameliorated tau hyperphosphorylation via PP2A, p35/25, and CDK5 pathways in N2a/APP cells. The amelioration of tau hyper phosphorylation by DAU was also validated in HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis revealed 85 differentially expressed proteins in the lysates between the wild-type N2a cells (N2a/WT) and the N2a/APP cells in the presence or absence of DAU; these were classified into 6 main categories according to their functions: endoplasmic reticulum (ER) stress-associated proteins, oxidative stress-associated proteins, cytoskeleton proteins, molecular chaperones, mitochondrial respiration and metabolism-related proteins, and signaling proteins. Taken together, we demonstrated that DAU treatment reduces AD-like pathology, thereby suggesting that DAU has potential therapeutic utility in AD.

Original languageEnglish (US)
Article number2025914
JournalOxidative medicine and cellular longevity
Volume2018
DOIs
StatePublished - 2018

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

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