title: [HIV-1 neuropathogenesis: therapeutic strategies against neuronal loss induced by gp120/Tat glycoprotein in the central nervous system].
abstract: Neuroinflammation is a key process in the neuropathogenesis of AIDS virus since as a result of the aberrant activation of the chemokine receptors (CXCR4, CX3CR1 and CR5) produces proinflammatory cytokine release by infected cells, increases microglial neurotoxicity and generates lipoperoxides and reactive oxygen species (ROS) that eventually damage the neuron. Moreover, the neurotoxin Tat produces dendritic loss by interacting with the low-density lipoprotein receptor (LRP) and also overstimulates N-methyl D-aspartate receptors (NMDA). Furthermore, the aberrant interaction of glycoprotein gp120 with the CXCR4 chemokine receptor causes caspase-3-dependent apoptosis (ceramide is also released) activating apoptotic proteins (p53 and retinoblastoma), which are part of the neurotoxic mechanisms associated to neuronal dysfunction in neuroAIDS. Similarly, gliosis/microglial activation and the release of neurotoxic factors by infected monocytes with elevated amounts of certain chemokines in the cerebrospinal fluid (MCP-1 and fractalkine, among others) contribute to the neuropathogenesis of HIV-1. Alpha-synuclein and beta amyloid deposits have also been detected in post mortem brains of seropositives patients. In addition, there are studies have detected several systemic markers related with the degenerative effects of the virus and its neurotoxins on the central nervous system; such as osteopontin, CD163 and fractalkine, among others. Lastly, clinical trials have been conducted using protective strategies related that attempt to inhibit apoptotic proteins (GSK-3 beta), microglial activation inhibitors (minocycline), antioxidants (selegiline) or trophic factors (IGF-1, growth hormone or erythropoietin). These trials have shown that their treatments are beneficial and complementary to treat complications of HIV/AIDS.
authors.affiliation: Instituto de Investigacion Sanitaria (IdiPaz). Hospital Universitario de La Paz (HULP), Madrid, Espana.
authors.forename: J J
authors.initials: JJ
authors.lastname: Merino
authors.forename: M L
authors.initials: ML
authors.lastname: Montes
authors.forename: A
authors.initials: A
authors.lastname: Blanco
authors.forename: M J
authors.initials: MJ
authors.lastname: Bustos
authors.forename: C
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: C
authors.initials: C
authors.lastname: Bayon
authors.forename: A
authors.initials: A
authors.lastname: Cuadrado
authors.forename: G
authors.initials: G
authors.lastname: Lubrini
authors.forename: I
authors.initials: I
authors.lastname: Cambron
authors.forename: A
authors.initials: A
authors.lastname: Munoz
authors.forename: S
authors.initials: S
authors.lastname: Cebolla
authors.forename: M
authors.initials: M
authors.lastname: Gutierrez-Fernandez
authors.forename: J I
authors.initials: JI
authors.lastname: Bernardino
authors.forename: J R
authors.initials: JR
authors.lastname: Arribas
authors.forename: M
authors.initials: M
authors.lastname: Fiala
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D002986:Clinical Trials as Topic; D004660:Encephalitis / Q000473:pathology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology* / Q000821:virology; D019718:Receptors, CXCR4 / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D054322:tat Gene Products, Human Immunodeficiency Virus