Journal
CELL STEM CELL
Volume 1, Issue 2, Pages 230-236Publisher
CELL PRESS
DOI: 10.1016/j.stem.2007.07.010
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NEI NIH HHS [R01 EY09024] Funding Source: Medline
- NINDS NIH HHS [R01 NS41207, R01 NS050621, P30 NS057096, R01 NS46994, R01 NS44326, R01 NS047973] Funding Source: Medline
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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 adult neural progenitor cells (aNPCs) in vitro and in vivo in the dentate gyrus of the hippocampus of HIV/gp120-transgenic mice. We demonstrate that HIV/gp120 arrests cell-cycle progression of aNPCs at the G1 phase via a cascade consisting of p38 mitogen-activated protein kinase (MAPK) -> MAPK-activated protein kinase 2 (a cell-cycle checkpoint kinase) -> Cdc25B/C. Our findings define a molecular mechanism that compromises adult neurogenesis in this neurodegenerative disorder.
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