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

作者：Tian, Xiao Lu; Yu, Lin Hui; Li, Wen Qin; Hu, Yue; Yin, Ming^*; Wang, Ze Jian

来源：Cellular and Molecular Neurobiology, 2015, 35(3): 425-432.

DOI：10.1007/s10571-014-0138-6

• 5-HT2C receptor
• Neprilysin
• Astrocyte
• Alzheimer's disease

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 Ab 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.

• 出版日期2015-4
• 单位上海交通大学