Cathepsin B: A cysteine protease associated with HIV-neurocognitive disorders and aging

Loyda M. Melendez

: J Antivir Antiretrovir

Abstract :

C hronic human immunodeficiency virus type one (HIV-1) infection leads to a spectrum of neurological and cognitive abnormalities, known collectively as HIV-associated neurocognitive disorders (HAND). HAND manifest in milder forms during despite effective combination antiretroviral therapy.The pathogenesis of HAND is thought to involve HIV-infected perivascular macrophages and microglia, whose activation leads to the release of pro-inflammatory cytokines and other soluble factors toxic to neurons. One factor that may be involved in macrophage-mediated HIV neurotoxicity is cathepsin B, a member of the cysteine protease family. We recently demonstrated that cathepsin B is upregulated in HIV-1 infected monocyte-derived macrophages (MDM), and secreted in a form that has increased neurotoxic activity in vitro and no longer interacted with its normal inhibitors, cystatin B and cystatin C. We recently observed increased expression of cathepsin B and cystatin B in monocytes of women with cognitive impairment, increased cathepsin B activity in plasma, and decreased cathepsin B activity in the CSF. A study of post-mortem brain tissue suggests that cathepsin B is also upregulated in brains from patients with HAND. We will present recent data related to the mechanisms whereby cathepsin B is dysregulated after HIV infection and how this dysregulation causes neuronal cell damage. This work was supported in part by NIH grants R01-MH08316-01, RCMI-NCRR- G12RR03051, SNRP-NINDS-1-U54NS431.

Biography :

Dr. Meléndez earned her Ph.D. degree in Experimental Pathology & Immunology cum laude from Emory University School of Medicine in 1990, where she also completed post-doctoral training in Hematology and Pediatric Infectious Diseases in collaboration with the Centers for Disease Control. Sheis a Professor in the Department of Microbiology, University of Puerto Rico School of Medicine. She directs the Viral Neuroimmunology Laboratory and the RCMI Translational Proteomics Center at the University of Puerto Rico Medical Sciences Campus (UPR-MSC). Dr. Meléndez is a co-inventor of one patent and has published over 30 manuscripts