HIV/AIDS Inhibits Neural Stem Cell Proliferation

A protein associated with AIDS prevents neural progenitors (stem cells) from replicating, according to a priority publication in Cancer Stem Cells. The protein's derogatory function may contribute to the onset of HIV-associated dementia and HIV/AIDSsome neurodegenerative diseases.

Burnham Institute scientists discovered that the protein, HIV/gp120, activates a pathway believed (.pdf) to play a role in Alzheimer's disease, ALS, Parkinson's disease, and multiple sclerosis. The neural progenitors still divide -- producing two cells with single-stranded DNA -- but HIV/gp120 prevents cells from forming the enzymes
necessary to rebuild the complementary strand of DNA necessary to have a functioning cell.

In mature nerve cells, the Burnham team had previously shown that HIV/gp120 activates the p38 MAPK pathway to contribute to cell death. Lipton and colleagues now report that the p38 MAPK pathway is also the mechanism underlying decreased stem cell proliferation in the brain associated with HIV/AIDS. Under experimental conditions, they were able to neutralize the p38 MAPK pathway and restore stem cell proliferation.

“We show for the first time how HIV/AIDS inhibits proliferation of neural stem cells and prevents the formation of new nerve cells in the adult brain,” said Dr. Stuart Lipton, Director of Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research.

“The fact that the mechanism of action involves the p38 MAPK enzyme is fortuitous because drugs to combat that pathway are being tested for other diseases. If they prove effective, they might also work to protect the brain. Thus, this study offers real hope for combating the bad effects of HIV/AIDS on stem cells in the brain.” Lipton went on to state, “It will be important to see if HIV/AIDS acts similarly on stem cells for other organs in the human body, as this may impact on the disease process as a whole.”

That would be a major finding if it is shown that the deleterious effects of HIV/AIDS are based solely on preventing stem cells from proliferating. Companies testing p38 MAPK inhibitors would have a whole new market open up to them.

AIDS Interferes with Stem Cells in the Brain [press release]

HIV/gp120 Decreases Adult Neural Progenitor Cell Proliferation via Checkpoint
Kinase-Mediated Cell-Cycle Withdrawal and G1 Arrest [Cancer Stem Cells]