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Cognitive dysfunction

Mitogen-activated protein kinase kinase kinase 11 (MAP3K11; MLK3)

Cell culture and mouse studies suggest the MLK3 inhibitor URMC-099 could be used to treat HIV-associated neurocognitive disorders (HAND). MLK3 has been associated with mediating neurotoxicity in mouse models for HIV-1 encephalitis. In cell-based and coculture models for HAND-associated neuroinflammation, URMC-099 decreased inflammatory cytokine levels and phagocytosis of axons compared with saline. In mouse models for HAND, URMC-099 decreased inflammatory cytokines and cortical dendritic spine elimination in the CNS compared with saline. Next steps include evaluating URMC-099 in a humanized mouse model for active HIV infection.

SciBX 6(26); doi:10.1038/scibx.2013.663
Published online July 11, 2013

Patent application filed; available for licensing

Marker, D.F. et al. J. Neurosci.; published online June 12, 2013;
Contact: Daniel F. Marker, University of Rochester, Rochester, N.Y.