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Encyclopedia of AIDS pp 1–6Cite as

HAND Adjunctive Therapies: Reversing Neuronal Injury

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This entry focuses on the therapeutic potential of small molecule inhibitors of two kinases, leucine-rich repeat kinase 2 (LRRK2) and mixed-lineage kinase 3 (MLK3), for the treatment of HIV-1-associated neurocognitive disorders (HAND). In particular, this entry is focused on these small molecule inhibitors as a way of restoring normal synaptic architecture, the key substrate that is damaged by the neuroinflammatory milieu of HAND.

From a signaling perspective, MLK3 is a canonical MAP kinase kinase kinase (MAPKKK) that controls the phosphorylation state of the MAPKs JNK and possibly p38 (Gallo and Johnson 2002). While only relatively recently implicated in the neuropathogenesis of Parkinson’s disease (PD), LRRK2 activation has also been strongly associated with neurodegeneration and neuroinflammation (Kim et al. 2012; Moehle et al. 2012), and studies of its mechanism of action demonstrate that it may also contribute to the phosphorylation of p38 and JNK (Hsu et al. 2010)....

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Author information

Authors and Affiliations

  1. Center for Neural Development and Disease, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, 14642, Rochester, NY, USA

    Daniel F. Marker & Timothy Fitzgerald

  2. Neurology in the Center for Neural Development & Disease, School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Ave, 645, 14642, Rochester, NY, USA

    Harris A. Gelbard

Authors
  1. Daniel F. Marker
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  2. Timothy Fitzgerald
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  3. Harris A. Gelbard
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Corresponding author

Correspondence to Harris A. Gelbard .

Editor information

Editors and Affiliations

  1. Dept. Cell & Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

    Thomas J. Hope

  2. Office of Graduate and Postdoctoral Studies, University of Miami, Miller School of Medicine, Miami, Florida, USA

    Mario Stevenson

  3. University of California, San Diego Dept. Pathology, La Jolla, California, USA

    Douglas Richman

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Marker, D.F., Fitzgerald, T., Gelbard, H.A. (2015). HAND Adjunctive Therapies: Reversing Neuronal Injury. In: Hope, T., Stevenson, M., Richman, D. (eds) Encyclopedia of AIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9610-6_217-1

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  • DOI: https://doi.org/10.1007/978-1-4614-9610-6_217-1

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  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-9610-6

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