HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest.
作者： Shu-ichi Okamoto , Yeon-Joo Kang , Christopher W. Brechtel , Elisa Siviglia , Rossella Russo
DOI: 10.1016/J.STEM.2007.07.010
关键词: Cell cycle 、 Biology 、 Neural stem cell 、 Progenitor cell 、 Neurogenesis 、 Dentate gyrus 、 Kinase 、 MAPK/ERK pathway 、 Protein kinase A 、 Cell biology
摘要: Summary Impaired adult neurogenesis has been observed in several neurodegenerative diseases, including human immunodeficiency virus (HIV-1)-associated dementia (HAD). Here we report that the HIV-envelope glycoprotein gp120, which is associated with HAD pathogenesis, inhibits proliferation of neural progenitor cells (aNPCs) vitro and vivo dentate gyrus hippocampus HIV/gp120-transgenic mice. We demonstrate HIV/gp120 arrests cell-cycle progression aNPCs at G1 phase via a cascade consisting p38 mitogen-activated protein kinase (MAPK) → MAPK-activated 2 (a checkpoint kinase) Cdc25B/C. Our findings define molecular mechanism compromises this disorder.
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