The purpose of this core is to assist in the design of adjunctive therapeutic strategies for treatment and/or prevention of neurologic disease following human immunodeficiency virus type-one (HIV-1) infection. In this regard, purified human monocyte-derived macrophages (MDM) and MDM conditioned media (MCM) will be supplied, following HIV-1 infection and/or immune activation, to all investigators on request, within the Rochester Cooperative NeuroAIDS Drug Discovery Group (RCNDDG). In addition, promising anti-inflammatory and/or neuroprotective drugs, developed in laboratory assays or proposed, will be tested for therapeutic efficacy in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Brain tissue and/or sera will be made available for measuring drug levels and pathology in the HIVE mice. Such works will support translational (bench to bedside) research efforts and directly effect the performance of subsequent clinical trials. The works, in toto, are based on the concept that HIV-1 associated dementia (HAD) is, in part, a reversible metabolic encephalopathy caused by defective immunity of virus-infected mononuclear phagocytes [(MP), microglia, perivascular and parenchymal macrophages]. These MPs serve both as reservoirs for productive HIV-1 infection and principal sources of neurotoxic activities within the central nervous system (CNS). The development of ways to inhibit toxic inflammatory activities in brain may serve to both ameliorate and prevent complications of persistent viral replication in brain serving as critical adjunctive therapies to ongoing potent anti-retroviral regimens, the principal goals of the RCNDDG.
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| Schutt, Charles R; Gendelman, Howard E; Mosley, R Lee (2018) Tolerogenic bone marrow-derived dendritic cells induce neuroprotective regulatory T cells in a model of Parkinson's disease. Mol Neurodegener 13:26 |
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| Thomas, Midhun B; Gnanadhas, Divya Prakash; Dash, Prasanta K et al. (2018) Modulating cellular autophagy for controlled antiretroviral drug release. Nanomedicine (Lond) 13:2139-2154 |
| Kiyota, Tomomi; Machhi, Jatin; Lu, Yaman et al. (2018) URMC-099 facilitates amyloid-? clearance in a murine model of Alzheimer's disease. J Neuroinflammation 15:137 |
| Kevadiya, Bhavesh D; Woldstad, Christopher; Ottemann, Brendan M et al. (2018) Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution. Theranostics 8:256-276 |
| McMillan, JoEllyn; Szlachetka, Adam; Slack, Lara et al. (2018) Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques. Antimicrob Agents Chemother 62: |
| Sillman, Brady; Woldstad, Christopher; Mcmillan, Joellyn et al. (2018) Neuropathogenesis of human immunodeficiency virus infection. Handb Clin Neurol 152:21-40 |
| Zhou, Tian; Su, Hang; Dash, Prasanta et al. (2018) Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials 151:53-65 |
| Kevadiya, Bhavesh D; Ottemann, Brendan M; Thomas, Midhun Ben et al. (2018) Neurotheranostics as personalized medicines. Adv Drug Deliv Rev : |
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