HIV-1 Protein Tat_(1–72) Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway

作     者：Yu Liu Deyu Zhou Jiabin Feng Zhou Liu Yue Hu Chang Liu Xiaohong Kong 

作者机构：Laboratory of Medical Molecular Virology School of Medicine Nankai University 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2018年第33卷第3期

页      面：261-269页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：supported by Grants from the National Natural Science Foundation of China (81571987) 

主　　题：Recombinant tat HIV-associated neurocognitive disorders (HAND) - Dendrite impairment - Proteinphosphatase 1 (PP1) CREB/BDNF 

摘      要：Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus(HIV)-associated neurocognitive disorders in people living with HIV-1 is increasing, significantly reducing the healthrelated quality of their lives. Although neurons cannot be infected by HIV-1, shed viral proteins such as transactivator of transcription(Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat(1–72 aa) induced neurotoxicity in primary cultured mouse neurons. Second, exposure to Tat_(1–72) was shown to reduce the length and number of dendrites in cultured neurons. Third, Tat_(1–72)(0–6 h) modulates protein phosphatase 1(PP1) expression and enhances its activity by decreasing the phosphorylation level of PP1 at Thr320. Finally, Tat_(1–72)(24 h) downregulates CREB activity and CREBmediated gene(BDNF, c-fos, Egr-1) expression. Together, these findings suggest that Tat_(1–72) might impair cognitive function by regulating the activity of PP1 and the CREB/BDNF pathway.