Skip to main content
SpringerLink
Log in

Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin

  • Part IV Neuroprotective Agents
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia can occur after infection with the human immunodeficiency virus-1 (HIV-1). Infected peripheral immune-competent cells, in particular macrophages, infiltrate the central nervous system (CNS) and provoke a neuropathological response involving all cell types in the brain. HIV-1 infection results in activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can trigger numerous downstream signaling pathways that result in disruption of neuronal and glial function. Despite many major improvements in the control of viral infection in the periphery, a truly effective therapy for HIV-1 associated dementia is currently not available. This review will discuss experimental and potentially future therapeutic strategies based on recently uncovered pathologic mechanisms contributing to neuronal damage induced by HIV-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adamson DC, B Wildemann, M Sasaki, JD Glass, JC McArthur, VI Christov, TM Dawson and VL Dawson (1996) Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41.Science 274, 1917–1921.

    PubMed  CAS  Google Scholar 

  • Adle-Biassette H, Y Levy, M Colombel, F Poron, S Natchev, C Keohane and F Gray (1995) Neuronal apoptosis in HIV infection in adults.Neuropathol. Appl. Neurobiol. 21, 218–227.

    PubMed  CAS  Google Scholar 

  • Adle-Biassette H, F Chretien, L Wingertsmann, C Hery, T Ereau, F Scaravilli, M Tardieu and F Gray (1999) Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage.Neuropathol. Appl. Neurobiol. 25, 123–133.

    PubMed  CAS  Google Scholar 

  • Agace WW, A Amara, AI Roberts, JL Pablos, S Thelen, M Uguccioni, XY Li, J Marsal, F Arenzana-Seisdedos, T Delaunay, EC Ebert, B Moser and CM Parker (2000) Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation.Curr. Biol. 10, 325–328.

    PubMed  CAS  Google Scholar 

  • Aizenman E, AK Stout, KA Hartnett, KE Dineley, B McLaughlin and IJ Reynolds (2000) Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular Zinc release.J. Neurochem. 75, 1878–1888.

    PubMed  CAS  Google Scholar 

  • Alkhatib G, C Combadiere, CC Broder, Y Feng, PE Kennedy, PM Murphy and EA Berger (1996) CC CKR5: a RANTES, MIP- 1alpha, MIP-1beta receptor as a fusion cofactor for macrophagetropic HIV-1.Science 272, 1955–1958.

    PubMed  CAS  Google Scholar 

  • Anderson ER, HE Gendelman and H Xiong (2004) Memantine protects hippocampal neuronal function in murine human immunodeficiency virus type 1 encephalitis.J. Neurosci. 24, 7194–7198.

    PubMed  CAS  Google Scholar 

  • Ankarcrona M, JM Dypbukt, E Bonfoco, B Zhivotovsk, S Orrenius, SA Lipton, and P Nicotera (1995) Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial integrity.Neuron 15, 961–973.

    PubMed  CAS  Google Scholar 

  • Arundine M and M Tymianski (2004) Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury.Cell. Mol. Life Sci. 61, 6578–668.

    Google Scholar 

  • Asensio VC and IL Campbell (1999) Chemokines in the CNS: plurifunctional mediators in diverse states.Trends Neurosci. 22, 504–512.

    PubMed  CAS  Google Scholar 

  • Bazan JF, KB Bacon, G Hardiman, W Wang, K Soo, D Rossi, DR Greaves, A Zlotnik and TJ Schall (1997) A new class of membrane-bound chemokine with a CX3C motif.Nature 385, 640–644.

    PubMed  CAS  Google Scholar 

  • Beckman JS, TW Beckman, J Chen, PA Marshall and BA Freeman (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proc. Natl. Acad. Sci. USA 87, 1620–1624.

    PubMed  CAS  Google Scholar 

  • Bezzi P, G Carmignoto, L Pasti, S Vesce, D Rossi, BL Rizzini, T Pozzan and A Volterra (1998) Prostaglandins stimulate calciumdependent glutamate release in astrocytes.Nature 391, 281–285.

    PubMed  CAS  Google Scholar 

  • Bezzi P, M Domercq, L Brambilla, R Galli, D Schols, E De Clercq, A Vescovi, G Bagetta, G Kollias, J Meldolesi and A Volterra (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity.Nat. Neurosci. 4, 702–710.

    PubMed  CAS  Google Scholar 

  • Bigge CF (1999) Ionotropic glutamate receptors.Curr. Opin. Chem. Biol. 3, 441–447.

    PubMed  CAS  Google Scholar 

  • Bleul CC, M Farzan, H Choe, C Parolin, I Clark-Lewis, J Sodroski and TA Springer (1996) The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry.Nature 382, 829–833.

    PubMed  CAS  Google Scholar 

  • Bonfoco E, D Krainc, M Ankarcrona, P Nicotera and SA Lipton (1995) Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures.Proc. Natl. Acad. Sci. USA 92, 7162–7166.

    PubMed  CAS  Google Scholar 

  • Bormann J (1989) Memantine is a potent blocker of N-methyl-Daspartate (NMDA) receptor channels.Eur. J. Pharmacol. 166, 591–592.

    PubMed  CAS  Google Scholar 

  • Bossy-Wetzel E, MV Talantova, WD Lee, MN Schölzke, A Harrop, E Mathews, T Götz, J Han, MH Ellisman, GA Perkins and SA Lipton (2004) Cross-talk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels.Neuron 41, 351–365.

    PubMed  CAS  Google Scholar 

  • Brack-Werner R and JE Bell (1999) Replication of HIV-1 in human astrocytes.Science Online: NeuroAids (www sciencemag org /NAIDS) 2, 1–7.

    Google Scholar 

  • Brauner-Osborne H, J Egebjerg, EO Nielsen, U Madsen and P Krogsgaard-Larsen (2000) Ligands for glutamate receptors: design and therapeutic prospects.J. Med. Chem. 43, 2609–2645.

    PubMed  CAS  Google Scholar 

  • Brenneman DE, GL Westbrook, SP Fitzgerald, DL Ennist, KL Elkins, MR Ruff and CB Pert (1988) Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide.Nature 335, 639–642.

    PubMed  CAS  Google Scholar 

  • Brew BJ, J Corbeil, L Pemberton, L Evans, K Saito, R Penny, DA Cooper and MP Heyes (1995) Quinolinic acid production is related to macrophage tropic isolates of HIV-1.J. Neurovirol. 1, 369–374.

    PubMed  CAS  Google Scholar 

  • Bruno V, A Copani, G Besong, G Scoto and F Nicoletti (2000) Neuroprotective activity of chemokines against N-methyl-Daspartate or beta-amyloid-induced toxicity in culture.Eur. J. Pharmacol. 399, 117–121.

    PubMed  CAS  Google Scholar 

  • Budd SL, L Tenneti, T Lishnak and SA Lipton (2000) Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons.Proc. Natl. Acad. Sci. USA 97, 6161–6166.

    PubMed  CAS  Google Scholar 

  • Budka H (1991) Neuropathology of human immunodeficiency virus infection.Brain Pathol. 1, 163–175.

    PubMed  CAS  Google Scholar 

  • Budka H, G Costanzi, S Cristina, A Lechi, C Parravicini, R Trabattoni and L Vago (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases.Acta Neuropathol. (Berl.) 75, 185–198.

    CAS  Google Scholar 

  • Celik M, N Gokmen, S Erbayraktar, M Akhisaroglu, S Konakc, C Ulukus, S Genc, K Genc, E Sagiroglu, A Cerami and M Brines (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury.Proc. Natl. Acad. Sci. USA 99, 2258–2263.

    PubMed  CAS  Google Scholar 

  • Chapman GA, K Moores, D Harrison, CA Campbell, BR Stewart and PJ Strijbos (2000) Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage.J. Neurosci. (Online)20, RC87.

    PubMed  CAS  Google Scholar 

  • Chen HS and SA Lipton (1997) Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism.J. Physiol. 499 (Pt. 1), 27–46.

    PubMed  CAS  Google Scholar 

  • Chen HS, JW Pellegrini, SK Aggarwal, SZ Lei, S Warach, FE Jensen and SA Lipton (1992) Open-channel block of N-methyl D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity.J. Neurosci. 12, 4427–4436.

    PubMed  CAS  Google Scholar 

  • Chen HS, YF Wang, PV Rayudu, P Edgecomb, JC Neill, MM Segal, SA Lipton and FE Jensen (1998) Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation.Neuroscience 86, 1121–1132.

    PubMed  CAS  Google Scholar 

  • Chen W, J Sulcove, I Frank, S Jaffer, H Ozdener and DL Kolson (2002) Development of a human neuronal cell model for human immunodeficiency virus (HIV)-infected macrophage-induced neurotoxicity: apoptosis induced by HIV type 1 primary isolates and evidence for involvement of the Bcl-2/Bcl-xL-sensitive intrinsic apoptosis pathway.J. Virol. 76, 9407–9419.

    PubMed  CAS  Google Scholar 

  • Choe H, M Farzan, Y Sun, N Sullivan, B Rollins, PD Ponath, L Wu, CR Mackay, G LaRosa, W Newman, N Gerard, C Gerard and J Sodroski (1996) The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.Cell 85, 1135–1148.

    PubMed  CAS  Google Scholar 

  • Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system.Neuron 1, 623–634.

    PubMed  CAS  Google Scholar 

  • Choi DW, JY Koh and S Peters (1988a) Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists.J. Neurosci. 8, 185–196.

    PubMed  CAS  Google Scholar 

  • Choi DW, M Yokoyama and J Koh (1988b) Zinc neurotoxicity in cortical cell culture.Neuroscience 24, 67–79.

    PubMed  CAS  Google Scholar 

  • Choi YB, L Tenneti, DA Le, J Ortiz, G Bai, HS Chen and SA Lipton (2000) Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation.Nat. Neurosci. 3, 15–21.

    PubMed  CAS  Google Scholar 

  • Choi YB, HS Chen and SA Lipton (2001) Three pairs of cysteine residues mediate both redox and Zn2+ modulation of the NMDA receptor.J. Neurosci. 21, 392–400.

    PubMed  CAS  Google Scholar 

  • Chung KK, B Thomas, X Li, O Pletnikova, JC Troncoso, L Marsh, VL Dawson and TM Dawson (2004) S-Nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function.Science 304, 1328–1331.

    PubMed  CAS  Google Scholar 

  • Clifford DB (1999) Central neurologic complications of HIV infection.Curr. Infect. Dis. Rep. 1, 187–191.

    PubMed  Google Scholar 

  • Clifford DB (2000) Human immunodeficiency virus-associated dementia.Arch. Neurol. 57, 321–324.

    PubMed  CAS  Google Scholar 

  • Cocchi F, AL Devico, A Garzino-Demo, SK Arya, RC Gallo and P Lusso (1995) Identification of RANTES, MIP-1 alpha, and MIP- 1 beta as the major HIV- suppressive factors produced by CD8+ T cells.Science 270, 1811–1815.

    PubMed  CAS  Google Scholar 

  • Conant K, A Garzino-Demo, A Nath, JC McArthur, W Halliday, C Power, RC Gallo and EO Major (1998) Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.Proc. Natl. Acad. Sci. USA 95, 3117–3121.

    PubMed  CAS  Google Scholar 

  • Cunningham PH, DG Smith, C Satchell, DA Cooper and B Brew (2000) Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid.AIDS 14, 1949–1954.

    PubMed  CAS  Google Scholar 

  • D’hooge R, F Franck, L Mucke and PP De Deyn (1999) Age-related behavioural deficits in transgenic mice expressing the HIV-1 coat protein gp120.Eur. J. Neurosci. 11, 4398–4402.

    PubMed  CAS  Google Scholar 

  • Das S, YF Sasaki, T Rothe, LS Premkumar, M Takasu, JE Crandall, P Dikkes, DA Conner, PV Rayudu, W Cheung, HS Chen, SA Lipton and N Nakanishi (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3a.Nature 393, 377–381.

    PubMed  CAS  Google Scholar 

  • Dawson VL, TM Dawson, ED London, DS Bredt and SH Snyder (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.Proc. Natl. Acad. Sci. USA 88, 6368–6371.

    PubMed  CAS  Google Scholar 

  • Dawson VL, TM Dawson, DA Bartley, GR Uhl and SH Snyder (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures.J. Neurosci. 13, 2651–2661.

    PubMed  CAS  Google Scholar 

  • De Clercq E (2004) HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.Int. J. Biochem. Cell. Biol. 36, 1800–1822.

    PubMed  Google Scholar 

  • Digicaylioglu M and SA Lipton (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades.Nature 412, 641–647.

    PubMed  CAS  Google Scholar 

  • Digicaylioglu M, G Garden, S Timberlake, L Fletcher and SA Lipton (2004a) Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I.Proc. Natl. Acad. Sci. USA 101, 9855–9860.

    PubMed  CAS  Google Scholar 

  • Digicaylioglu M, M Kaul, L Fletcher, R Dowen and SA Lipton (2004b) Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage.Neuroreport 15, 761–763.

    PubMed  Google Scholar 

  • Dimmeler S, J Haendeler, M Nehls and AM Zeiher (1997) Suppression of apoptosis by nitric oxide via inhibition of interleukin-1beta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases.J. Exp. Med. 185, 601–607.

    PubMed  CAS  Google Scholar 

  • Doble A (1999) The role of excitotoxicity in neurodegenerative disease: implications for therapy.Pharmacol. Ther. 81, 163–221.

    PubMed  CAS  Google Scholar 

  • Doranz BJ, J Rucker, Y Yi, RJ Smyth, M Samson, SC Peiper, M Parmentier, RG Collman and RW Doms (1996) A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR5, CKR3, and CKR2b as fusion cofactors.Cell 85, 1149–1158.

    PubMed  CAS  Google Scholar 

  • Dore GJ, JF Hoy, SA Mallal, Y Li, AM Mijch, MA French, DA Cooper and JM Kaldor (1997) Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort.J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 16, 39–43.

    PubMed  CAS  Google Scholar 

  • Dore GJ, PK Correll, Y Li, JM Kaldor, DA Cooper and BJ Brew (1999) Changes to AIDS dementia complex in the era of highly active antiretroviral therapy.AIDS 13, 1249–1253.

    PubMed  CAS  Google Scholar 

  • Dragic T, V Litwin, GP Allaway, SR Martin, Y Huang, KA Nagashima, C Cayanan, PJ Maddon, RA Koup, JP Moore and WA Paxton (1996) HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.Nature 381, 667–673.

    Google Scholar 

  • Dreyer EB and SA Lipton (1995) The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid.Eur. J. Neurosci. 7, 2502–2507.

    PubMed  CAS  Google Scholar 

  • Dreyer EB, PK Kaiser, JT Offermannand SA Lipton (1990) HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists.Science 248, 364–367.

    PubMed  CAS  Google Scholar 

  • Ellis RJ, R Deutsch, RK Heaton, TD Marcotte, JA McCutchan, JA Nelson, I Abramson, LJ Thal, JH Atkinson, MR Wallace and I Grant (1997) Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.Arch. Neurol. 54, 416–424.

    PubMed  CAS  Google Scholar 

  • Enting RH, RM Hoetelmans, JM Lange, DM Burger, JH Beijnen and P Portegies (1998) Antiretroviral drugs and the central nervous system.AIDS 12, 1941–1955.

    PubMed  CAS  Google Scholar 

  • Erdo SL and M Schafer (1991) Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate.Eur. J. Pharmacol. 198, 215–217.

    PubMed  CAS  Google Scholar 

  • Everall IP, RK Heaton, TD Marcotte, RJ Ellis, JA McCutchan, JH Atkinson, I Grant, M Mallory and E Masliah (1999) Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC group. HIV Neurobehavioral Research Center.Brain Pathol. 9, 209–217.

    PubMed  CAS  Google Scholar 

  • Ferrando S, W van Gorp, M McElhiney, K Goggin, M Sewell and J Rabkin (1998) Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function.AIDS 12, F65-F70.

    PubMed  CAS  Google Scholar 

  • Fiala M, DJ Looney, M Stins, DD Way, L Zhang, X Gan, F Chiappelli, ES Schweitzer, P Shapshak, M Weinand, MC Graves, M Witte and KS Kim (1997) TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier.Mol. Med. 3, 553–564.

    PubMed  CAS  Google Scholar 

  • Fischer-Smith T, S Croul, AE Sverstiuk, C Capini, D L’Heureux, EG Regulier, MW Richardson, S Amini, S Morgello, K Khalili and J Rappaport (2001) CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection.J. Neurovirol. 7, 528–541.

    PubMed  CAS  Google Scholar 

  • Fontana G, L Valenti and M Raiteri (1997) gp120 can revert antagonism at the glycine site of NMDA receptors mediating GABA release from cultured hippocampal neurons.J. Neurosci. Res. 49, 732–738.

    PubMed  CAS  Google Scholar 

  • Fox L, M Alford, C Achim, M Mallory and E Masliah (1997) Neurodegeneration of somatostatin-immunoreactive neurons in HIV encephalitis.J. Neuropathol. Exp. Neurol. 56, 360–368.

    PubMed  CAS  Google Scholar 

  • Gabuzda DH, DD Ho, SM de la Monte, MS Hirsch, TR Rota and RA Sobel (1986) Immunohistochemical identification of HTLVIII antigen in brains of patients with AIDS.Ann. Neurol. 20, 289–295.

    PubMed  CAS  Google Scholar 

  • Galasso JM, JK Harrison and FS Silverstein (1998) Excitotoxic brain injury stimulates expression of the chemokine receptor CCR5 in neonatal rats.Am. J. Pathol. 153, 1631–1640.

    PubMed  CAS  Google Scholar 

  • Garden GA, SL Budd, E Tsai, L Hanson, M Kaul, DM D’Emilia, RM Friedlander, J Yuan, E Masliah and SA Lipton (2002) Caspase cascades in human immunodeficiency virus-associated neurodegeneration.J. Neurosci. 22, 4015–4024.

    PubMed  CAS  Google Scholar 

  • Garden GA, W Guo, S Jayadev, C Tun, S Balcaitis, J Choi, TJ Montine, T Moller and RS Morrison (2004) HIV associated neurodegeneration requires p53 in neurons and microglia.FASEB J. 18, 1141–1143.

    PubMed  CAS  Google Scholar 

  • Gartner S (2000) HIV infection and dementia.Science 287, 602–604.

    PubMed  CAS  Google Scholar 

  • Gelbard HA, HJ James, LR Sharer, SW Perry, Y Saito, AM Kazee, BM Blumberg and LG Epstein (1995) Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy.Neuropathol. Appl. Neurobiol. 21, 208–217.

    PubMed  CAS  Google Scholar 

  • Gendelman HE, I Grant, SA Lipton, I Everall and S Swindells (2005)The Neurology of AIDS (Oxford University Press: London), 1184 pp.

    Google Scholar 

  • Genis P, M Jett, EW Bernton, T Boyle, HA Gelbard, K Dzenko, RW Keane, L Resnick, Y Mizrachi, DJ Volskyet al. (1992) Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.J. Exp. Med. 176, 1703–1718.

    PubMed  CAS  Google Scholar 

  • Ghatan S, S Larner, Y Kinoshita, M Hetman, L Patel, Z Xia, RJ Youle and RS Morrison (2000) p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons.J. Cell. Biol. 150, 335–347.

    PubMed  CAS  Google Scholar 

  • Giulian D, K Vacaand CA Noonan (1990) Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1.Science 250, 1593–1596.

    PubMed  CAS  Google Scholar 

  • Giulian D, E Wendt, K Vaca and CA Noonan (1993) The envelope glycoprotein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes.Proc. Natl. Acad. Sci. USA 90, 2769–2773.

    PubMed  CAS  Google Scholar 

  • Giulian D, J Yu, X Li, D Tom, J Li, E Wendt, SN Lin, R Schwarcz and C Noonan (1996) Study of receptor-mediated neurotoxins released by HIV-1 infected mononuclear phagocytes found in human brain.J. Neurosci. 16, 3139–3153.

    PubMed  CAS  Google Scholar 

  • Glass JD, H Fedor, SL Wesselingh and JC McArthur (1995) Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia.Ann. Neurol. 38, 755–762.

    PubMed  CAS  Google Scholar 

  • Gleichmann M, C Gillen, M Czardybon, F Bosse, R Greiner-Petter, J Auer and HW Muller (2000) Cloning and characterization of SDF-1gamma, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system.Eur. J. Neurosci. 12, 1857–1866.

    PubMed  CAS  Google Scholar 

  • Gonzalez-Zulueta M, AB Feldman, LJ Klesse, RG Kalb, JF Dillman, LF Parada, TM Dawson and VL Dawson (2000) Requirement for nitric oxide activation of p21(ras)/extracellular regulated kinase in neuronal ischemic preconditioning.Proc. Natl. Acad. Sci. USA 97, 436–441.

    PubMed  CAS  Google Scholar 

  • Gu Z, M Kaul, B Yan, SJ Kridel, J Cui, A Strongin, JW Smith, RC Liddington and SA Lipton (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death.Science 297, 1186–1190.

    PubMed  CAS  Google Scholar 

  • He J, Y Chen, M Farzan, H Choe, A Ohagen, S Gartner, J Busciglio, X Yang, W Hofmann, W Newman, CR Mackay, J Sodroski and D Gabuzda (1997) CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia.Nature 385, 645–649.

    PubMed  CAS  Google Scholar 

  • Hesselgesser J, D Taub, P Baskar, M Greenberg, J Hoxie, DL Kolson and R Horuk (1998) Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4.Curr. Biol. 8, 595–598.

    PubMed  CAS  Google Scholar 

  • Heyes MP, BJ Brew, A Martin, RW Price, AM Salazar, JJ Sidtis, JA Yergey, MM Mouradian, AE Sadler, J Keilp, D Rubinow and SP Markey (1991) Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status.Ann. Neurol. 29, 202–209.

    PubMed  CAS  Google Scholar 

  • Jain KK (2000) Evaluation of memantine for neuroprotection in dementia.Expert Opin. Investig. Drugs 9, 1397–1406.

    PubMed  CAS  Google Scholar 

  • Jiang ZG, C Piggee, MP Heyes, C Murphy, B Quearry, M Bauer, J Zheng, HE Gendelman and SP Markey (2001) Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1- infected macrophages.J. Neuroimmunol. 117, 97–107.

    PubMed  CAS  Google Scholar 

  • Johnston JB, Y Jiang, G van Marle, MB Mayne, W Ni, J Holden, JC McArthur and C Power (2000) Lentivirus infection in the brain induces matrix metalloproteinase expression: role of envelope diversity.J. Virol. 74, 7211–7220.

    PubMed  CAS  Google Scholar 

  • Kaul M (2002) Chemokines and their receptors in HIV-associated dementia.J. Neurovirol. 8 (suppl. 1), 41–42.

    Google Scholar 

  • Kaul M and SA Lipton (1999) Chemokines and activated macrophages in gp120-induced neuronal apoptosis.Proc. Natl. Acad. Sci. USA 96, 8212–8216.

    PubMed  CAS  Google Scholar 

  • Kaul M and SA Lipton (2001) Knock out of HIV-1 coreceptors attenuates neuronal apoptosis induced by HIV envelope glycoprotein gp120. Soc. Neurosci. 27, 678.8 (Abstr.).

    Google Scholar 

  • Kaul M, GA Garden and SA Lipton (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia.Nature 410, 988–994.

    PubMed  CAS  Google Scholar 

  • Kaul M, J Zheng, S Okamoto, HE Gendelman and SA Lipton (2005) HIV-1 infection and AIDS: consequences for the central nervous system.Cell Death Differ. 12 (Suppl. 1), 878–892.

    PubMed  CAS  Google Scholar 

  • Keilhoff G and G Wolf (1992) Memantine prevents quinolinic acid-induced hippocampal damage.Eur. J. Pharmacol. 219, 1

    Google Scholar 

  • Kikuchi M, L Tenneti and SA Lipton (2000) Role of p38 mitogenactivated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells.J. Neurosci. 20, 5037–5044.

    PubMed  CAS  Google Scholar 

  • Kim WK, YB Choi, PV Rayudu, P Das, W Asaad, DR Arnelle, JS Stamler and SA Lipton (1999) Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-.Neuron 24, 461–469.

    PubMed  CAS  Google Scholar 

  • Koenig S, HE Gendelman, JM Orenstein, MC Dal Canto, GH Pezeshkpour, M Yungbluth, F Janotta, A Aksamit, MA Martin and AS Fauci (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.Science 233, 1089–1093.

    PubMed  CAS  Google Scholar 

  • Kohr G, S Eckardt, H Luddens, H Monyer and PH Seeburg (1994) NMDA receptor channels: subunit-specific potentiation by reducing agents.Neuron 12, 1031–1040.

    PubMed  CAS  Google Scholar 

  • Krathwohl MD and JL Kaiser (2004a) Chemokines promote quiescence and survival of human neural progenitor cells.Stem Cells 22, 109–118.

    PubMed  CAS  Google Scholar 

  • Krathwohl MD and JL Kaiser (2004b) HIV-1 promotes quiescence in human neural progenitor cells.J. Infect. Dis. 190, 216–226.

    PubMed  CAS  Google Scholar 

  • LangfordD, VJ Sanders, M Mallory, M Kaul and E Masliah (2002) Expression of stromal cell-derived factor 1alpha protein in HIV encephalitis.J. Neuroimmunol. 127, 115–126.

    PubMed  CAS  Google Scholar 

  • Lannuzel A, PM Lledo, HO Lamghitnia, JD Vincent and M Tardieu (1995) HIV-1 envelope proteins gp120 and gp160 potentiate NMDA [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons.Eur. J. Neurosci. 7, 2285–2293.

    PubMed  CAS  Google Scholar 

  • Lapidot T and I Petit (2002) Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells.Exp. Hematol. 30, 973–981.

    PubMed  CAS  Google Scholar 

  • Le D, S Das, YF Wang, T Yoshizawa, YF Sasaki, M Takasu, A Nemes, M Mendelsohn, P Dikkes, SA Lipton and N Nakanishi (1997) Enhanced neuronal death from focal ischemia in AMPAreceptor transgenic mice.Brain Res. Mol. Brain Res. 52, 235–241.

    PubMed  CAS  Google Scholar 

  • Le DA and SA Lipton (2001) Potential and current use of N-methyl- D-aspartate (NMDA) receptor antagonists in diseases of aging.Drugs Aging 18, 717–724.

    PubMed  CAS  Google Scholar 

  • Lees KR (1997) Cerestat and other NMDA antagonists in ischemic stroke.Neurology 49, S66-S69.

    PubMed  CAS  Google Scholar 

  • Lei SZ, ZH Pan, SK Aggarwal, HS Chen, J Hartman, NJ Sucher and SA Lipton (1992) Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex.Neuron 8, 1087–1099.

    PubMed  CAS  Google Scholar 

  • Letendre SL, ER Lanier and JA McCutchan (1999) Cerebrospinal fluid beta chemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1.J. Infect. Dis. 180, 310–319.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1991a) Calcium channel antagonists and human immunodeficiency virus coat protein-mediated neuronal injury.Ann. Neurol. 30, 110–114.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1991b) Calcium channel antagonists in the prevention of neurotoxicity.Adv. Pharmacol. 22, 271–297.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1992a) Memantine prevents HIV coat protein-induced neuronal injuryin vitro.Neurology 42, 1403–1405.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1992b) Models of neuronal injury in AIDS: another role for the NMDA receptor?Trends Neurosci. 15, 75–79.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1992c) Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120.Neuroreport 3, 913–915.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1993) Prospects for clinically tolerated NMDA antagonists: open-channel blockers and alternative redox states of nitric oxide.Trends Neurosci. 16, 527–532.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1994a) HIV coat protein gp120 induces soluble neurotoxins in culture medium.Neurosci. Res. Commun. 15, 31–37.

    CAS  Google Scholar 

  • Lipton SA (1994b) HIV displays its coat of arms.Nature 367, 113–114 [Erratum 367, 320].

    PubMed  CAS  Google Scholar 

  • Lipton SA (1997a) Neuropathogenesis of acquired immunodeficiency syndrome dementia.Curr. Opin. Neurol. 10, 247–253.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1997b) Treating AIDS dementia [letter; comment].Science 276, 1629–1630.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1998) Neuronal injury associated with HIV-1: approaches to treatment.Annu. Rev. Pharmacol. Toxicol. 38, 159–177.

    PubMed  CAS  Google Scholar 

  • Lipton SA (2004a) Erythropoietin for neurologic protection and diabetic neuropathy.N. Engl. J. Med. 350, 2516–2517.

    PubMed  CAS  Google Scholar 

  • Lipton SA (2004b) Concepts: turning down but not off — Neuroprotection requires a paradigm shift in drug development.Nature 428, 473.

    PubMed  CAS  Google Scholar 

  • Lipton SA (2004c) Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults.NeuroRx 1, 101–110.

    PubMed  Google Scholar 

  • Lipton SA (2005) The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: low affinity, uncompetitive antagonism.Curr. Alzheim. Res. 2(2), 155–165.

    CAS  Google Scholar 

  • Lipton SA and H-SV Chen (2004) Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine.Cell Death Diff. 11, 18–20.

    CAS  Google Scholar 

  • Lipton SA and HE Gendelman (1995) Seminars in Medicine of the Beth Israel Hospital, Boston. Dementia associated with the acquired immunodeficiency syndrome.N. Engl. J. Med. 332, 934–940.

    PubMed  CAS  Google Scholar 

  • Lipton SA and FE Jensen (1992) Memantine, a clinically-tolerated NMDA open-channel blocker, prevents HIV coat proteininduced neuronal injuryin vitro andin vivo. Soc. Neurosci.18, 757 (Abstr.).

    Google Scholar 

  • Lipton SA and K Kieburtz (1998) Development of adjunctive therapies for the neurologic manifestations of AIDS: dementia and painful neuropathy, In:The Neurology of AIDS (Gendelman HE, SA Lipton, LG Epstein and S Swindells, Eds.) (Chapman and Hall: New York), pp 377–381.

    Google Scholar 

  • Lipton SA and P Nicotera (1998) Calcium, free radicals and excitotoxins in neuronal apoptosis.Cell Calcium 23, 165–171.

    PubMed  CAS  Google Scholar 

  • Lipton SA and PA Rosenberg (1994) Excitatory amino acids as a final common pathway for neurologic disorders.N. Engl. J. Med. 330, 613–622.

    PubMed  CAS  Google Scholar 

  • Lipton SA and JS Stamler (1994) Actions of redox-related congeners of nitric oxide at the NMDA receptor.Neuropharmacology 33, 1229–1233.

    PubMed  CAS  Google Scholar 

  • Lipton SA, Y-B Choi, ZH Pan, SZ Lei, H-SV Chen, NJ Sucher, J Loscalzo, DJ Singel and JS Stamler (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds.Nature 364, 626–632.

    PubMed  CAS  Google Scholar 

  • Lipton SA, Y-B Choi, T Takahashi, D Zhang, W Li, A Godzik and LA Bankston (2002) Cysteine regulation of protein function - as exemplified by NMDA-receptor modulation.Trends Neurosci. 25, 474–480.

    PubMed  CAS  Google Scholar 

  • Lipton SA, NJ Sucher, PK Kaiser and EB Dreyer (1991) Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity.Neuron 7, 111–118.

    PubMed  CAS  Google Scholar 

  • Lipton SA and YF Wang (1996) NO-related species can protect from focal cerebral ischemia/reperfusion, In:Pharmacology of Cerebral Ischemia (Krieglstein J, Ed.) (Medpharm Scientific Publ.: Stuttgart), pp 183–191.

    Google Scholar 

  • Lipton SA, T Nakamura, D Yao, Z-Q Shi, T Uehara and Z Gu (2005) Comment on S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function.Science 308 (5730), 1870; author reply 1870.

    PubMed  CAS  Google Scholar 

  • Liu R, WA Paxton, S Choe, D Ceradini, SR Martin, R Horuk, ME MacDonald, H Stuhlmann, RA Koup and NR Landau (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.Cell 86, 367–377.

    PubMed  CAS  Google Scholar 

  • Liu Y, M Jones, CM Hingtgen, G Bu, N Laribee, RE Tanzi, RD Moir, A Nath and JJ He (2000) Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands.Nat. Med. 6, 1380–1387.

    PubMed  CAS  Google Scholar 

  • Lo TM, CJ Fallert, TM Piser and SA Thayer (1992) HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons.Brain Res. 594, 189–196.

    PubMed  CAS  Google Scholar 

  • Locati M and PM Murphy (1999) Chemokines and chemokine receptors: biology and clinical relevance in inflammation and AIDS.Annu. Rev. Med. 50, 425–440.

    PubMed  CAS  Google Scholar 

  • Lucas DR and JP Newhouse (1957) The toxic effect of sodium L-glutamate on the inner layers of the retina.AMA Arch. Ophthalmol. 58, 193–201.

    PubMed  CAS  Google Scholar 

  • Ma Q, D Jones, PR Borghesani, RA Segal, T Nagasawa, T Kishimoto, RT Bronson and TA Springer (1998) Impaired Blymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice.Proc. Natl. Acad. Sci. USA 95, 9448–9453.

    PubMed  CAS  Google Scholar 

  • Major EO, D Rausch, C Marra and D Clifford (2000) HIV-associated dementia.Science 288, 440–442.

    PubMed  CAS  Google Scholar 

  • Mannick JB, A Hausladen, L Liu, DT Hess, M Zeng, QX Miao, LS Kane, AJ Gow and JS Stamler (1999) Fas-induced caspase denitrosylation.Science 284, 651–654.

    PubMed  CAS  Google Scholar 

  • Marshall DC, T Wyss-Coray and CR Abraham (1998) Induction of matrix metalloproteinase-2 in human immunodeficiency virus- 1 glycoprotein 120 transgenic mouse brains.Neurosci. Lett. 254, 97–100.

    PubMed  CAS  Google Scholar 

  • Masliah E, N Ge, CL Achim, LA Hansen and CA Wiley (1992) Selective neuronal vulnerability in HIV encephalitis.J. Neuropathol. Exp. Neurol. 51, 585–593.

    PubMed  CAS  Google Scholar 

  • Masliah E, RK Heaton, TD Marcotte, RJ Ellis, CA Wiley, M Mallory, CL Achim, JA McCutchan, JA Nelson, JH Atkinson and I Grant(1997) Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC group. The HIV Neurobehavioral Research Center.Ann. Neurol. 42, 963–972.

    PubMed  CAS  Google Scholar 

  • Masuda S, M Nagao, K Takahata, Y Konishi, F Gallyas Jr, T Tabira and R Sasaki (1993) Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells.J. Biol. Chem. 268, 11208–11216.

    PubMed  CAS  Google Scholar 

  • McArthur JC (1987) Neurologic manifestations of AIDS.Medicine (Baltimore) 66, 407–437.

    CAS  Google Scholar 

  • McArthur JC, DR Hoover, H Bacellar, EN Miller, BA Cohen, JT Becker, NM Graham, JH McArthur, OA Selnes and LP Jacobson (1993) Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study.Neurology 43, 2245–2252.

    PubMed  CAS  Google Scholar 

  • McArthur JC, DR McClernon, MF Cronin, TE Nance-Sproson, AJ Saah, M St Clair and ER Lanier (1997) Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain.Ann. Neurol. 42, 689–698.

    PubMed  CAS  Google Scholar 

  • McGrath KE, AD Koniski, KM Maltby, JK McGann and J Palis (1999) Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4.Dev. Biol. 213, 442–456.

    PubMed  CAS  Google Scholar 

  • Melino G F Bernassola, RA Knight, MT Corasaniti, G Nistico and A Finazzi-Agro (1997) S-nitrosylation regulates apoptosis.Nature 388, 432–433.

    Google Scholar 

  • Melton ST, CK Kirkwood and SN Ghaemi (1997) Pharm-acotherapy of HIV dementia.Ann. Pharmacother. 31, 457–473.

    PubMed  CAS  Google Scholar 

  • Mennicken F, R Maki, EB de Souza and R Quirion (1999) Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning.Trends Pharmacol. Sci. 20, 73–78.

    PubMed  CAS  Google Scholar 

  • Meucci O, A Fatatis, AA Simen, TJ Bushell, PW Gray and RJ Miller (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity.Proc. Natl. Acad. Sci. USA 95, 14500–14505.

    PubMed  CAS  Google Scholar 

  • Michael NL and JP Moore (1999) HIV-1 entry inhibitors: evading the issue [news] [see comments].Nat. Med. 5, 740–742.

    PubMed  CAS  Google Scholar 

  • Moore RD, JC Keruly and RE Chaisson (1998) Anemia and survival in HIV infection.J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 19, 29–33.

    PubMed  CAS  Google Scholar 

  • Morishita E, S Masuda, M Nagao, Y Yasuda and R Sasaki (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin preventsin vitro glutamate-induced neuronal death.Neuroscience 76, 105–116.

    PubMed  CAS  Google Scholar 

  • Mukherjee PK, MA DeCoster, FZ Campbell, RJ Davis and NG Bazan (1999) Glutamate receptor signaling interplay modulates stress-sensitive mitogen-activated protein kinases and neuronal cell death.J. Biol. Chem. 274, 6493–6498.

    PubMed  CAS  Google Scholar 

  • Muller WE, HC Schroder, H Ushijima, J Dapper and J Bormann (1992) Gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.Eur. J. Pharmacol. 226, 209–214.

    PubMed  CAS  Google Scholar 

  • Navia BA, U Dafni, D Simpson, T Tucker, E Singer, JC McArthur, C Yiannoutsos, L Zaborski and SA Lipton (1998) A phase I/II trial of nimodipine for HIV-related neurologic complications.Neurology 51, 221–228.

    PubMed  CAS  Google Scholar 

  • Navia BA, C Yiannoutsos, R Ellis, G Schifitto, A Nath, S Shriver, L Millar and SA Lipton (2005) Memantine may prevent further cognitive decline in subjects with the AIDS Dementia Complex with detectable CSF HIV RNA.Neurology 64 (Suppl. 1), A247-A238.

    Google Scholar 

  • Nicotera P, M Ankarcrona, E Bonfoco, S Orrenius and SA Lipton (1997) Neuronal necrosis and apoptosis: two distinct events induced by exposure to glutamate or oxidative stress.Adv. Neurol. 72, 95–101.

    PubMed  CAS  Google Scholar 

  • Nottet HS, Y Persidsky, VG Sasseville, AN Nukuna, P Bock, QH Zhai, LR Sharer, RD McComb, S Swindells, C Soderland and HE Gendelman (1996) Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain.J. Immunol. 156, 1284–1295.

    PubMed  CAS  Google Scholar 

  • Oberlin E, A Amara, F Bachelerie, C Bessia, JL Virelizier, F Arenzana-Seisdedos, O Schwartz, JM Heard, I Clark-Lewis, DF Legler, M Loetscher, M Baggiolini and B Moser (1996) The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.Nature 382, 833–835.

    PubMed  CAS  Google Scholar 

  • Ohagen A, S Ghosh, J He, K Huang, Y Chen, M Yuan, R Osathanondh, S Gartner, B Shi, G Shaw and D Gabuzda (1999) Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope.J. Virol. 73, 897–906.

    PubMed  CAS  Google Scholar 

  • Okamoto S, Z Li, C Ju, MN Scholzke, E Mathews, J Cui, GS Salvesen, E Bossy-Wetzel and SA Lipton (2002) Dominantinterfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis.Proc. Natl. Acad. Sci. USA 99, 3974–3979.

    PubMed  CAS  Google Scholar 

  • Olney JW (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.Science 164, 719–721.

    PubMed  CAS  Google Scholar 

  • Olney JW and LG Sharpe (1969) Brain lesions in an infant rhesus monkey treated with monsodium glutamate.Science 166, 386–388.

    PubMed  CAS  Google Scholar 

  • Orgogozo J-M, A-S Rigaud, A Stöffler, H-J Möbius and F Forette (2002) Efficacy and safety of memantine in patients with mild to moderate vascular dementia - a randomized, placebo-controlled trial (MMM 300).Stroke 33, 1834–1839.

    PubMed  CAS  Google Scholar 

  • Osborne NN and G Quack (1992) Memantine stimulates inositol phosphates production in neurones and nullifies N-methyl-Daspartate-induced destruction of retinal neurones.Neurochem. Int. 21, 329–336.

    PubMed  CAS  Google Scholar 

  • Parsons CG, W Danysz and G Quack (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data.Neuropharmacology 38, 735–767.

    PubMed  CAS  Google Scholar 

  • Paxton WA, R Liu, S Kang, L Wu, TR Gingeras, NR Landau, CR Mackay and RA Koup (1998) Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines.Virology 244, 66–73.

    PubMed  CAS  Google Scholar 

  • Pellegrini JW and SA Lipton (1993) Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity.Ann. Neurol. 33, 403–407.

    PubMed  CAS  Google Scholar 

  • Petito CK and B Roberts (1995) Evidence of apoptotic cell death in HIV encephalitis.Am. J. Pathol. 146, 1121–1130.

    PubMed  CAS  Google Scholar 

  • Pierson TC, RW Doms and S Pohlmann (2004) Prospects of HIV-1 entry inhibitors as novel therapeutics.Rev. Med. Virol. 14, 255–270.

    PubMed  CAS  Google Scholar 

  • Piot P, M Bartos, PD Ghys, N Walker and B Schwartlander (2001) The global impact of HIV/AIDS.Nature 410, 968–973.

    PubMed  CAS  Google Scholar 

  • Pittaluga A, R Pattarini, P Severi and M Raiteri (1996) Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120.AIDS 10, 463–468.

    PubMed  CAS  Google Scholar 

  • Power C, JC McArthur, A Nath, K Wehrly, M Mayne, J Nishio, T Langelier, RT Johnson and B Chesebro (1998) Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients.J. Virol. 72, 9045–9053.

    PubMed  CAS  Google Scholar 

  • Power C, MJ Gilland RT Johnson (2002) Progress in clinical neurosciences: the neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy.Can. J. Neurol. Sci. 29, 19–32.

    PubMed  CAS  Google Scholar 

  • Reisberg B, R Doody, A Stöffler, F Schmitt, S Ferris and HF Möbius (2003) Memantine in moderate-to-severe Alzheimer’s disease.N. Engl. J. Med. 348, 1333–1341.

    PubMed  CAS  Google Scholar 

  • Rottman JB, KP Ganley, K Williams, L Wu, CR Mackay and DJ Ringler (1997) Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am. J. Pathol.151, 1341–1351.

    PubMed  CAS  Google Scholar 

  • Sacktor N, RH Lyles, R Skolasky, C Kleeberger, OA Selnes, EN Miller, JT Becker, B Cohen and JC McArthur (2001) HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998.Neurology 56, 257–260.

    PubMed  CAS  Google Scholar 

  • Sadamoto Y, K Igase, M Sakanaka, K Sato, H Otsuka, S Sakaki, S Masuda and R Sasaki (1998) Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery.Biochem. Biophys. Res. Commun. 253, 26–32.

    PubMed  CAS  Google Scholar 

  • Samson M, F Libert, BJ Doranz, J Rucker, C Liesnard, CM Farber, S Saragosti, C Lapoumeroulie, J Cognaux, C Forceille, G Muyldermans, C Verhofstede, G Burtonboy, M Georges, T Imai, S Rana, Y Yi, RJ Smyth, RG Collman, RW Doms, G Vassart and M Parmentier (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR5 chemokine receptor gene.Nature 382, 722–725.

    PubMed  CAS  Google Scholar 

  • Sardar AM, PH Hutson and GP Reynolds (1999) Deficits of NMDA receptors and glutamate uptake sites in the frontal cortex in AIDS.Neuroreport 10, 3513–3515.

    PubMed  CAS  Google Scholar 

  • Sathi S, P Edgecomb, S Warach, K Manchester, T Donaghey, PE Stieg, FE Jensen and SA Lipton 1993 Chronic transdermal nitroglycerin (NTG) is neuroprotective in experimental rodent stroke models.Soc. Neurosci.19, 849 (Abstr.).

    Google Scholar 

  • Sattler R,Z Xiong, WY Lu, M Hafner, JF MacDonald and M Tymianski (1999) Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein.Science 284, 1845–1848.

    PubMed  CAS  Google Scholar 

  • Savio T and G Levi (1993) Neurotoxicity of HIV coat protein gp120, NMDA receptors, and protein kinase C: a study with rat cerebellar granule cell cultures.J. Neurosci. Res. 34, 265–272.

    PubMed  CAS  Google Scholar 

  • Scala E, G D’Offizi, R Rosso, O Turriziani, R Ferrara, AM Mazzone, G Antonelli, F Aiuti and R Paganelli (1997) C-C chemokines, IL- 16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection.J. Immunol. 158, 4485–4492.

    PubMed  CAS  Google Scholar 

  • Schifitto G, N Sacktor, K Marder, MP McDermott, JC McArthur, K Kieburtz, S Small and LG Epstein (1999) Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.Neurology 53, 391–396.

    PubMed  CAS  Google Scholar 

  • Schulzer M, E Mak and DB Calne (1992) The antiparkinson efficacy of depreyl derives from transient improvement that is likely to be symptomatic.Ann. Neurol. 32, 795–798.

    PubMed  CAS  Google Scholar 

  • Seif nel Nasr M, B Peruche, C Rossberg, HD Mennel and J Krieglstein (1990) Neuroprotective effect of memantine demonstratedin vivo andin vitro.Eur. J. Pharmacol. 185, 19–24.

    Google Scholar 

  • Simmons G, D Wilkinson, JD Reeves, MT Dittmar, S Beddows, J Weber, G Carnegie, U Desselberger, PW Gray, RA Weiss and PR Clapham (1996) Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry.J. Virol. 70, 8355–8360.

    PubMed  CAS  Google Scholar 

  • Sinor AD and DA Greenberg (2000) Erythropoietin protects cultured cortical neurons, but not astroglia, from hypoxia and AMPA toxicity.Neurosci. Lett. 290, 213–215.

    PubMed  CAS  Google Scholar 

  • Stieg PE, S Sathi, S Warach, DA Le and SA Lipton (1999) Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat.Eur. J. Pharmacol. 375, 115–120.

    PubMed  CAS  Google Scholar 

  • Stumm RK, J Rummel, V Junker, C Culmsee, M Pfeiffer, J Krieglstein, V Hollt and S Schulz (2002) A dual role for the SDF- 1/CXCR4 chemokine receptor system in adult brain: isoformselective regulation of SDF-1 expression modulates CXCR4- dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia.J. Neurosci. 22, 5865–5878.

    PubMed  CAS  Google Scholar 

  • Sullivan JM, SF Traynelis, HS Chen, W Escobar, SF Heinemann and SA Lipton (1994) Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor.Neuron 13, 929–936.

    PubMed  CAS  Google Scholar 

  • Susman E (2001) Memantine improves function and cognition i advanced Alzheimer’s.Inpharma Weekly 1292, 5.

    Google Scholar 

  • Tachibana K,S Hirota, H Iizasa, H Yoshida, K Kawabata, Y Kataoka, Y Kitamura, K Matsushima, N Yoshida, S Nishikawa, T Kishimoto and T Nagasawa (1998) The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.Nature 393, 591–594.

    PubMed  CAS  Google Scholar 

  • Tariot PN, MR Farlow, GT Grossberg, SM Graham, S McDonald and I Gergel (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.JAMA 291, 317–324.

    PubMed  CAS  Google Scholar 

  • Tenneti L, DM D’Emilia and SA Lipton (1997) Suppression of neuronal apoptosis by S-nitrosylation of caspases.Neurosci. Lett. 236, 139–142.

    PubMed  CAS  Google Scholar 

  • Tenneti L, DM D’Emilia, CM Troy and SA Lipton (1998) Role of caspases in N-methyl-D-aspartate-induced apoptosis in cerebrocortical neurons.J. Neurochem. 71, 946–959.

    PubMed  CAS  Google Scholar 

  • Toggas SM, E Masliah, EM Rockenstein, GF Rall, CR Abraham and L Mucke (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice.Nature 367, 188–193.

    PubMed  CAS  Google Scholar 

  • Toggas SM, E Masliah and L Mucke (1996) Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine.Brain Res. 706, 303–307.

    PubMed  CAS  Google Scholar 

  • Tran PB and RJ Miller (2003) Chemokine receptors: signposts to brain development and disease.Nat. Rev. Neurosci. 4, 444–455.

    PubMed  CAS  Google Scholar 

  • Turchan J, N Sacktor, V Wojna, K Conant and A Nath (2003) Neuroprotective therapy for HIV dementia.Curr. HIV Res. 1, 373–383.

    PubMed  CAS  Google Scholar 

  • Verani A and P Lusso (2002) Chemokines as natural HIV antagonists.Curr. Mol. Med. 2, 691–702.

    PubMed  CAS  Google Scholar 

  • Wang H, S-W Yu, DW Koh, J lew, C Coombs, W Bowers, HJ Federoff, GG Poirier, TM Dawson and VL Dawson (2004) Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered excitotoxic neuronal death.J. Neurosci. 24, 10963–10973.

    PubMed  CAS  Google Scholar 

  • Weiss JH and SL Sensi (2000) Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration.Trends Neurosci. 23, 365–371.

    PubMed  CAS  Google Scholar 

  • Wen TC, Y Sadamoto, J Tanaka, PX Zhu, K Nakata, YJ Ma, R Hata and M Sakanaka (2002) Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression.J. Neurosci. Res. 67, 795–803.

    PubMed  CAS  Google Scholar 

  • Wesselingh SL, K Takahashi, JD Glass, JC McArthur, JW Griffin and DE Griffin (1997) Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reactionin situ hybridization and immunohistochemistry.J. Neuroimmunol. 74, 1–8.

    PubMed  CAS  Google Scholar 

  • Wiley CA, V Soontornniyomkij, L Radhakrishnan, E Masliah, J Mellors, SA Hermann, P Dailey and CL Achim (1998) Distribution of brain HIV load in AIDS.Brain Pathol. 8, 277–284.

    PubMed  CAS  Google Scholar 

  • Yao D, Z Gu, T Nakamura, Z-Q Shi, Y Ma, B Gaston, LA Palmer, EM Rockenstein, Z Zhang, E Masliah, T Uehara and SA Lipton (2004) Nitrosative stress linked to sporadic Parkinson’s disease: S-nitrosylation of parkin regulates it E3 ligase activity.Proc. Natl. Acad. Sci. USA 101, 10810–10814.

    PubMed  CAS  Google Scholar 

  • Yeh MW, M Kaul, J Zheng, HS Nottet, M Thylin, HE Gendelman and SA Lipton (2000) Cytokine-stimulated, but not HIV-infected, human monocyte-derived macrophages produce neurotoxic levels of L-cysteine.J. Immunol. 164, 4265–4270.

    PubMed  CAS  Google Scholar 

  • Zagury D, A Lachgar, V Chams, LS Fall, J Bernard, JF Zagury, B Bizzini, A Gringeri, E Santagostino, J Rappaport, M Feldman, SJ O’Brien, A Burny and RC Gallo (1998) C-C chemokines, pivotal in protection against HIV type 1 infection.Proc. Natl. Acad. Sci. USA 95, 3857–3861.

    PubMed  CAS  Google Scholar 

  • Zhang K, GA McQuibban, C Silva, GS Butler, JB Johnston, J Holden, I Clark-Lewis, CM Overall and C Power (2003) HIVinduced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration.Nat. Neurosci. 6, 1064–1071.

    PubMed  CAS  Google Scholar 

  • Zhang L, T He, A Talal, G Wang, SS Frankel and DD Ho (1998)In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5.J. Virol. 72, 5035–5045.

    PubMed  CAS  Google Scholar 

  • Zhao J, AL Lopez, D Erichsen, S Herek, RL Cotter, NP Curthoys and J Zheng (2004) Mitochondrial glutaminase enhances extracellular glutamate production in HIV-1-infected macrophages: linkage to HIV-1 associated dementia.J. Neurochem. 88, 169–180.

    PubMed  CAS  Google Scholar 

  • Zheng J, MR Thylin, A Ghorpade, H Xiong, Y Persidsky, R Cotter, D Niemann, M Che, YC Zeng, HA Gelbard, RB Shepard, JM Swartz and HE Gendelman (1999) Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia.J. Neuroimmunol. 98, 185–200.

    PubMed  CAS  Google Scholar 

  • Zou YR, AH Kottmann, M Kuroda, I Taniuchi and DR Littman (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development.Nature 393, 595–599.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, 92037, La Jolla, CA, USA

    Marcus Kaul & Stuart A. Lipton

Authors
  1. Marcus Kaul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stuart A. Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Marcus Kaul or Stuart A. Lipton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaul, M., Lipton, S.A. Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin. neurotox res 8, 167–186 (2005). https://doi.org/10.1007/BF03033828

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033828

Keywords

Search

Navigation