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Activation of 5-HT2C Receptor Promotes the Expression of Neprilysin in U251 Human Glioma Cells

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Abstract

Abeta accumulation, a hallmark of Alzheimer’s disease, promotes the disease progress in multiple facets. Abeta is formed through amyloidogenic cleavage pathway of amyloid precursor protein (APP). Production of Abeta can be decreased via activation of 5-HT2C receptor, which enhances alternative APP non-amyloidogenic cleavage. Besides, as one of the best characterized Aβ degrading enzymes, neprilysin (NEP) in AD progress has drawn more and more attention. We investigated whether there exists any connection between 5-HT2C receptor and NEP expression. The mRNA and protein expressions of NEP were increased after treatment of 5-HT2C receptor agonist RO-60-0175 in concentration- and time-dependent manners, and NEP expression was decreased after treatment of 5-HT2C receptor antagonist SB242084 correspondingly. These results suggest that 5-HT2C receptor may inhibit the Abeta formation by promoting NEP expression. The underlying mechanism will be explored in follow-up study and may provide potential target for AD therapy.

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Acknowledgments

This Project was supported by the National Natural Science Foundation of China (Grants Number: 81270432), and Science and technology innovation Grant of Shanghai Jiaotong University (Grants Number: 14X130040002).

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Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China

    Xiao-Lu Tian, Lin-Hui Yu, Wen-Qin Li, Yue Hu, Ming Yin & Ze-Jian Wang

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  1. Xiao-Lu Tian
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  2. Lin-Hui Yu
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  3. Wen-Qin Li
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  4. Yue Hu
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Correspondence to Ming Yin or Ze-Jian Wang.

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Tian, XL., Yu, LH., Li, WQ. et al. Activation of 5-HT2C Receptor Promotes the Expression of Neprilysin in U251 Human Glioma Cells. Cell Mol Neurobiol 35, 425–432 (2015). https://doi.org/10.1007/s10571-014-0138-6

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