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

Format:

Book

Thesis/Dissertation

Author/Creator:

Cook, Denise R.

Contributor:

Lynch, David R., committee member.

Kalb, Robert G., committee member.

Crino, Peter B., committee member.

Neumar, Robert W., committee member.

Kolson, Dennis L., advisor.

University of Pennsylvania. Neuroscience.

Language:

English

Subjects (All):

Virology.

Neurosciences.

Biology, Neuroscience.

Biology, Virology.

0317.

0720.

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Local Subjects:

Biology, Neuroscience.

Biology, Virology.

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

0317.

0720.

Physical Description:

172 pages

Contained In:

Dissertation Abstracts International 74-03B(E).

System Details:

Mode of access: World Wide Web.

text file

Summary:

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.

Notes:

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 2012.

Source: Dissertation Abstracts International, Volume: 74-03(E), Section: B.

Adviser: Dennis L. Kolson.

Local Notes:

School code: 0175.

ISBN:

9781267712622

Access Restriction:

Restricted for use by site license.