Neuroprotective roles for apelin, a novel neuropeptide, in HIV-associated excitotoxic injury

Denise R Cook, University of Pennsylvania


Human immunodeficiency virus (HIV) infection of the central nervous system can cause neurodegeneration and associated cognitive, motor, and behavioral abnormalities collectively known as HIV-associated neurocognitive disorders (HAND). HAND remains prevalent despite improved antiretroviral drug therapies, and adjunctive neuroprotective therapies are clearly needed. Excitotoxic neuronal damage via over-activation of the N-methyl-D-aspartate (NMDA) receptor may be the final common pathway of injury in HAND, and accordingly, further understanding of endogenous mechanisms that regulate NMDA receptors and excitotoxicity is critical for the development of effective neuroprotective therapies. Herein, we identify apelin, the endogenous neuropeptide ligand for the G-protein coupled receptor APJ, as a unique neuroprotective target against excitotoxicity. Our studies with exogenous apelin define a novel apelinergic signaling pathway that concurrently activates pro-survival signaling and inhibits NMDA receptor-mediated excitotoxic signaling to protect neurons against excitotoxicity. Our studies with endogenous apelin demonstrate that excitotoxicity modulates apelin expression and release from neurons, and that endogenous soluble apelin can limit neurodegeneration. Together, our work defining apelin-mediated neuroprotection advances our understanding of neuroprotective pathways and will potentially improve our ability to develop therapeutics for HAND and other excitotoxicity-associated neurodegenerative disorders.

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Recommended Citation

Cook, Denise R, "Neuroprotective roles for apelin, a novel neuropeptide, in HIV-associated excitotoxic injury" (2012). Dissertations available from ProQuest. AAI3542793.