Activation of c-Jun N-terminal kinase mediates gp120IIIB- and nucleoside analogue-induced sensory neuron toxicity

Experimental Neurology
Amos BodnerRichard J Miller

Abstract

Peripheral neuropathy is the most common neurological symptom in patients with acquired immunodeficiency syndrome (AIDS). Here, we examine possible mechanisms of gp120 and nucleoside reverse transcriptase inhibitors (NRTIs) in the pathogenesis of AIDS peripheral neuropathy. Neonatal dorsal root ganglion (DRG) neurons were found to undergo apoptosis in response to chronic treatment with gp120IIIB, an effect enhanced by the co-application of hCD4, as well as upon exposure to the nucleoside reverse transcriptase inhibitor (NRTI), 2',3'-dideoxyinosine (ddI). DRG neurons were rescued from the neurotoxic effects of these agents by CEP-1347, an inhibitor of the mixed lineage kinases (MLKs), upstream activators of the c-Jun N-terminal kinase (JNK) signaling pathway. In addition, gp120- or ddI-mediated toxicity were also inhibited by neuronal expression of dominant negative versions of the MLKs. Our results suggest that both gp120 and the NRTIs cause sensory neuron apoptosis through the activation of the JNK pathway, and that CEP-1347-like compounds may serve as a therapeutic option in patients with AIDS-associated peripheral neuropathy.

References

Dec 1, 1992·Journal of the Neurological Sciences·O RonchiF Mazzotta
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C A WileyM B Oldstone
Apr 1, 1995·Trends in Pharmacological Sciences·S A LiptonL Mucke
Feb 18, 1995·Lancet·E J Cupler, M C Dalakas
Dec 1, 1993·The Journal of Physiology·P S ChardR J Miller
Apr 1, 1993·Journal of Neurology, Neurosurgery, and Psychiatry·G N FullerR J Guiloff
Aug 17, 1996·Lancet·R W Price
Nov 1, 1996·The Journal of Clinical Investigation·B ShiD Gabuzda
Jun 1, 1997·Current Opinion in Neurology·S A Lipton
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·C E BazenetL L Rubin
Apr 1, 1998·Journal of Neuroimmunology·L M BolinK B Bacon
May 23, 1998·Annual Review of Pharmacology and Toxicology·S A Lipton
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·O MeucciR J Miller
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·M Kaul, S A Lipton
Apr 11, 2001·Journal of the Peripheral Nervous System : JPNS·C A PardoJ W Griffin
Apr 28, 2001·The Journal of Biological Chemistry·A C MaroneyJ L Vaught
Jul 12, 2001·Toxicology and Applied Pharmacology·U Namgung, Z Xia
Oct 2, 2002·Journal of Neurochemistry·Amos BodnerRichard J Miller
Jan 2, 2003·Annals of Neurology·Sanjay C KeswaniAhmet Hoke
Feb 26, 2003·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Catherine L CherrySteven L Wesselingh
Apr 23, 2003·Journal of Neurovirology·Justin C McArthurNed Sacktor
Jul 17, 2003·Journal of Neuroimmunology·Amos BodnerRichard J Miller
Sep 4, 2003·Annals of Neurology·Sanjay C KeswaniAhmet Hoke
Oct 4, 2003·Nature Reviews. Drug Discovery·William LewisWilliam C Copeland
Oct 21, 2006·Biochemical Society Transactions·A J Whitmarsh

❮ Previous
Next ❯

Citations

Nov 2, 2005·Neurotoxicity Research·P B Tran, R J Miller
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kurt F HauserPamela E Knapp
Nov 22, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Elizabeth M PodhaizerKurt F Hauser
Sep 29, 2011·Neurotoxicity Research·Italo MocchettiValeriya Avdoshina
Oct 1, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Harris A GelbardHoward E Gendelman
Jun 14, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniel F MarkerHarris A Gelbard
Jun 6, 2013·Journal of Neurovirology·Qing MaGiovanni Schifitto
Jul 27, 2010·Expert Opinion on Drug Discovery·Giorgia Melli, Ahmet Höke
May 6, 2008·Neuroscience Letters·Yong-Jing Gao, Ru-Rong Ji
Apr 2, 2009·Journal of the Peripheral Nervous System : JPNS·Ahmet HökeNorman J Haughey
May 1, 2007·European Journal of Pain : EJP·Corinne G JolivaltNigel A Calcutt
Apr 3, 2012·Journal of the Peripheral Nervous System : JPNS·Peter R KamermanWenlong Huang
Jan 27, 2015·Neuroscience Letters·Christopher R Cashman, Ahmet Höke
Sep 14, 2006·Current Opinion in Neurology·David R Cornblath, Ahmet Hoke
Sep 17, 2014·Current Opinion in HIV and AIDS·Howard E Gendelman, Harris A Gelbard
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ziye SuiSanjay B Maggirwar
Sep 24, 2019·Frontiers in Cellular Neuroscience·Andrew SpeidellItalo Mocchetti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis