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Therefore, blocking gp120 neurotoxicity may be an effective way to reduce the neuronal degeneration seen in HIV patients. Brain\u2010derived neurotrophic factor (BDNF) prevents gp120\u2010mediated apoptosis in cerebellar granule cells. However, BDNF poorly crosses the blood\u2013brain barrier and therefore may not be a suitable therapy for HIV patients. LIGA20 is a semisynthetic sphingoglycolipid that may be a valid alternative to BDNF. In fact, it has been shown that LIGA20 mimics the neuroprotective properties of BDNF. The present study was undertaken to characterize the relative potency of LIGA20 to antagonize gp120\u2010mediated apoptosis. Cerebellar granule cells were exposed to gp120IIIB (5 nM) or stromal\u2010cell derived factor\u20101 (SDF), the natural ligand for the CXCR4 receptor to which gp120 binds, alone or in combination with LIGA20 (5 \u03bcM), and cell death\/survival was determined 12 and 24 hr later by various markers of apoptosis. LIGA20 blocked the neurotoxic effect of gp120 and SDF. The neurotrophic effect of LIGA20 was reversed by K252a, a tyrosine kinase inhibitor used to block TrkB signaling, suggesting the involvement of TrkB activation. These findings provide the rationale for exploring the ability of compounds that mimic BDNF activity to reduce neuronal cell death in HIV\u20101\u2010positive patients. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20780","type":"journal-article","created":{"date-parts":[[2006,2,13]],"date-time":"2006-02-13T21:47:14Z","timestamp":1139867234000},"page":"890-896","source":"Crossref","is-referenced-by-count":17,"title":["Semisynthetic sphingoglycolipid LIGA20 is neuroprotective against human immunodeficiency virus\u2010gp120\u2010mediated 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