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Polyphyllin I attenuates cognitive impairments and reduces AD‐like pathology through CIP2A‐PP2A signaling pathway in 3XTg‐AD mice
Author(s) -
Zhou Ying,
Yang Dichen,
Chen Hao,
Zheng Chenfei,
Jiang Huanchang,
Liu Xiaoyuan,
Huang Xingzhou,
Ye Simin,
Song Shuangshuang,
Jiang Nan,
Zhao Zhongyuan,
Ma Shuqing,
Ma Jun,
Huang Kate,
Chen Chaosheng,
Fan Xiaofang,
Gong Yongsheng,
Wang Xiaochuan,
Fan Junming,
Liu Rong,
Shentu Yangping
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001499r
Subject(s) - protein phosphatase 2 , hyperphosphorylation , downregulation and upregulation , phosphorylation , cancer research , medicine , microbiology and biotechnology , biology , phosphatase , gene , biochemistry
Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor‐inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application of PPI in experimental AD treatment in CIP2A‐overexpressed cells and 3XTg‐AD mice. In CIP2A‐overexpressed HEK293 cells or primary neurons, PPI effectively reduced CIP2A level, activated PP2A, and decreased the phosphorylation of tau/APP and the level of Aβ. Furthermore, synaptic protein levels were restored by PPI in primary neurons overexpressing CIP2A. Animal experiments in 3XTg‐AD mice revealed that PPI treatment resulted in decreased CIP2A expression and PP2A re‐activation. With the modification of CIP2A‐PP2A signaling, the hyperphosphorylation of tau/APP and Aβ overproduction were prevented, and the cognitive impairments of 3XTg‐AD mice were rescued. In summary, PPI ameliorated AD‐like pathology and cognitive impairment through modulating CIP2A‐PP2A signaling pathway. It may be a potential drug candidate for the treatment of AD.