Abstract
The treatment of HIV infection presents a great challenge among the patients who develop various forms of cognitive impairments. Particularly, the neurotoxicity associated with HIV is attributed to different viral proteins present in HIV, and is a root cause for HIV-associated neurocognitive disorders (HAND). A common characteristic among several neurodegenerative disorders including HAND is mitochondrial dysfunction in various brain cells. However, there has been very little effort to explore the possibility of exploiting mitochondrial dynamics in HAND treatment. A recent study by Avdoshina and colleagues has reported the role of mitochondrial dysfunction in HIV-1 gp120-mediated neuronal dysfunction, which presents a novel mechanism for the development of adjunct therapy to treat HAND.
Similar content being viewed by others
References
Adle-Biassette H, Levy Y, Colombel M, Poron F, Natchev S, Keohane C, Gray F (1995) Neuronal apoptosis in HIV infection in adults. Neuropathol Appl Neurobiol 21:218–227
Antinori A et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799. doi:10.1212/01.WNL.0000287431.88658.8b
Avdoshina V, Fields JA, Castellano P, Dedoni S, Palchik G, Trejo M, Adame A, Rockenstein E, Eugenin E, Masliah E, Mocchetti I (2016) The HIV protein gp120 alters mitochondrial dynamics in neurons. Neurotox Res 29(4):583–593
Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA, Ganie SA (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 74:101–110. doi:10.1016/j.biopha.2015.07.025
del Palacio M, Alvarez S, Munoz-Fernandez MA (2012) HIV-1 infection and neurocognitive impairment in the current era. Rev Med Virol 22:33–45. doi:10.1002/rmv.711
Gelman BB (2015) Neuropathology of HAND with suppressive antiretroviral therapy: encephalitis and neurodegeneration reconsidered. Curr HIV/AIDS Rep 12:272–279. doi:10.1007/s11904-015-0266-8
Haughey NJ, Mattson MP (2002) Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. J Acquir Immune Defic Syndr 31(Suppl 2):55–61
Kaul M (2008) HIV’s double strike at the brain: neuronal toxicity and compromised neurogenesis. Front Biosci 13:2484–2494
Kitayama H, Miura Y, Ando Y, Hoshino S, Ishizaka Y, Koyanagi Y (2008) Human immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through induction of mitochondrial dysfunction. J Virol 82:2528–2542. doi:10.1128/JVI.02094-07
Lee J (2016) Mitochondrial drug targets in neurodegenerative diseases. Bioorg Med Chem Lett 26:714–720. doi:10.1016/j.bmcl.2015.11.032
Lehmann HC, Chen W, Borzan J, Mankowski JL, Hoke A (2011) Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy. Ann Neurol 69:100–110. doi:10.1002/ana.22150
Li W, Galey D, Mattson MP, Nath A (2005) Molecular and cellular mechanisms of neuronal cell death in HIV dementia. Neurotox Res 8:119–134
Li W, Li G, Steiner J, Nath A (2009) Role of Tat protein in HIV neuropathogenesis. Neurotox Res 16:205–220. doi:10.1007/s12640-009-9047-8
Lindl KA, Marks DR, Kolson DL, Jordan-Sciutto KL (2010) HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol 5:294–309. doi:10.1007/s11481-010-9205-z
Pagano G et al (2014) Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies. Oxid Med Cell Longev 2014:541230. doi:10.1155/2014/541230
Reynolds A, Laurie C, Mosley RL, Gendelman HE (2007) Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol 82:297–325. doi:10.1016/S0074-7742(07)82016-2
Sacktor N (2002) The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 8(Suppl 2):115–121. doi:10.1080/13550280290101094
Silverstein PS, Shah A, Weemhoff J, Kumar S, Singh DP, Kumar A (2012) HIV-1 gp120 and drugs of abuse: interactions in the central nervous system. Curr HIV Res 10:369–383
Stevens PR, Gawryluk JW, Hui L, Chen X, Geiger JD (2014) Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury. Curr HIV Res 12:378–387
Villeneuve LM, Purnell PR, Stauch KL, Callen SE, Buch SJ, Fox HS (2016) HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution. J Neurovirol. doi:10.1007/s13365-016-0424-9
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shah, A., Kumar, A. HIV-1 gp120-Mediated Mitochondrial Dysfunction and HIV-Associated Neurological Disorders. Neurotox Res 30, 135–137 (2016). https://doi.org/10.1007/s12640-016-9619-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-016-9619-3