How HIV Infection Kills Brain Cells

The authors found that when certain immune cells (called macrophages) were infected with HIV-1, they released a substance toxic to neurons. Further examination revealed that the substance, an inactive form of a protein called matrix metalloprotease 2 (MMP2), was itself not the killer, but rather was converted by neurons into an enzyme that cleaves another protein, called stromal-derived factor (SDF) 1. SDF-1 has a number of normal functions in the brain, but the shortened form of SDF-1 was highly toxic to neurons. Rats given the inactive MMP2 showed loss of neurons and exhibited behavioral problems. By using drugs that block the activation of MMP2 (and thus the cleavage of SDF-1), the researchers could diminish the toxic effects. Such MMP2 inhibitors are already in clinical trials for cancer.

Author contact:

Christopher Power
University of Calgary, Alberta, Canada
Tel: +1 403 220 5572
E-mail: power@ucalgary.ca

Additional contact for comment on paper:

Richard Ransohoff
Lerner Research Institute, Cleveland, Ohio, USA
Tel: +1 216 444 0627
E-mail: ransohr@ccf.org

Also available online.

(C) Nature Neuroscience press release.

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