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Oxid Med Cell Longev. 2018 Jul 2;2018:2025914. doi: 10.1155/2018/2025914. eCollection 2018.

The Isoquinoline Alkaloid Dauricine Targets Multiple Molecular Pathways to Ameliorate Alzheimer-Like Pathological Changes In Vitro.

Author information

1
College of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, China.
2
Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
3
Department of Encephalopathy, Shaanxi University of Chinese Medicine, Xianyang, Shanxi 712000, China.
4
Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou 510632, China.
5
Cognitive Impairment Ward of Neurology Department, The 3rd Affiliated Hospital of Shenzhen University, Shenzhen 518055, China.
6
Department of Neurology, Second Clinical College, Jinan University, Shenzhen 518020, China.
7
Department of Neurology, School of Medicine, Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239, USA.

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 hyperphosphorylation 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.

PMID:
30057671
PMCID:
PMC6051032
DOI:
10.1155/2018/2025914
[Indexed for MEDLINE]
Free PMC Article

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