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Human Immunodeficiency Virus

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Microglia in Health and Disease

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Abstract

Microglia have been known to be the resident immune cells in the brain for quite some time, but their role as pathologic players in neurological infectious disease has only recently been studied. For example, microglial activation has recently been shown to be a strong driver of neurological impairment in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND). Studying the interactions between microglia and synaptic networks during chronic HIV infection is pivotal to understanding why normal synaptic communication is impaired and is the etiologic substrate for HIV-associated neurocognitive deficits, despite successful control of viral replication by combination antiretroviral therapy (cART). In this chapter we focus on the phenomenology of these interactions and suggest that upregulation of mixed lineage kinase type 3 (MLK3) and leucine-rich repeat kinase 2 (LRRK2) activity plays a pivotal role in microglial activation and synaptic dysfunction that give rise to HAND. We further discuss the rationale for targeting pathologic activation of these kinases in creating disease-modifying strategies for the treatment of HAND.

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Acknowledgments

This work was funded by NIH P30 AI078498 (H.A.G.), PO1 MH64570 (H.A.G.), NIH RO1 MH56838 (H.A.G.), NIH UL1 RR024160 (H.A.G.), NIH T32 GM07356 (D.F.M.), NIH T32 AI049815 (D.F.M.), NIH F30 MH095664 (D.F.M.), and the Geoffrey Waisdorp Pediatric Neurology Fund (H.A.G.).

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  1. Center for Neural Development and Disease, Department of Neurology (Child Neurology Division), University of Rochester Medical Center, 645, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Daniel F. Marker Ph.D., Shao-Ming Lu Ph.D. & Harris A. Gelbard M.D., Ph.D.

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  1. Daniel F. Marker Ph.D.
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  2. Shao-Ming Lu Ph.D.
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  3. Harris A. Gelbard M.D., Ph.D.
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Correspondence to Harris A. Gelbard M.D., Ph.D. .

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  1. Axe Neurosciences, Centre de recherche du, CHU de Québec, and Department of Molecular Medicine, Université Laval, Québec, Québec, Canada

    Marie-Ève Tremblay

  2. Achucarro Basque Center for Neuroscience, University of the Basque Country, EHU/UPV, Ikerbasque Foundation, Zamudio, Bizkaia, Spain

    Amanda Sierra

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Marker, D.F., Lu, SM., Gelbard, H.A. (2014). Human Immunodeficiency Virus. In: Tremblay, MÈ., Sierra, A. (eds) Microglia in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1429-6_15

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