HIV-1 Protein Tat1-72 Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway

• 来源期刊: 中国病毒学
• 年，卷（期）: 2018,（3）
• 页码范围: 261-269
• 页数: 9页
• 语种: 英文

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 health-related 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 Tat1-72 was shown to reduce the length and number of dendrites in cultured neurons.Third,Tat1-72 (0-6 h) modulates protein phosphatase 1 (PP1) expression and enhances its activity by decreasing the phosphorylation level of PP1 at Thr320.Finally,Tat1-72 (24 h) downregulates CREB activity and CREB-mediated gene (BDNF,c-fos,Egr-1) expression.Together,these findings suggest that Tat1-72 might impair cognitive function by regulating the activity of PP1 and the CREB/BDNF pathway.