Dr. Pravin C. Singal and colleagues at the Feinstein Institute for Medical Research, Manhasset, NY; the Texas Health Science Center, San Antonio, Texas; and New York Medical College, Valhalla, NY have identified mammalian target of rapamycin (mTOR) as a therapeutic target for HIV-associated nephropathy.
These results are presented in the August 2010 issue of the American Journal of Pathology.
HIV-associated nephropathy, or kidney disease that develops in association with HIV infection, usually occurs only with advanced disease. HIV-associated nephropathy may be caused by direct HIV-1 infection in the renal cells, with resulting renal damage through the viral gene products, or by changes in the release of inflammatory molecules during HIV infection.
HIV-associated nephropathy is characterized by cell proliferation in affected kidney lesions. To determine if mTOR, which plays a key role in cell growth, was involved in this proliferative phenotype, Kumar et al examined mTOR activation in a mouse model of the disease. Both mTOR and its downstream targets were activated at higher levels in diseased mice as compared with controls, indicating enhanced activation of the mTOR signaling pathway. In addition, both mTOR activation and renal disease could be blocked by treatment with rapamycin, which inhibits the mTOR pathway. This report therefore supports mTOR as a therapeutic target for HIV-associated nephropathy.
Dr. Singal's group concludes that "mTOR pathway activation is contributing to both the proliferative phenotype as well as to the development of [HIV-associated nephropathy."
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