title: Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine.
abstract: A unique feature of N-methyl-D-aspartate receptors (NMDARs) that distinguishes them from other ionic receptors is that their activation requires more than one agonist to bind simultaneously to distinct binding sites on the receptor. D-serine, a co-agonist binding to the glycine site of NMDARs, has been implicated in several NMDAR-dependent physiological processes, and altered D-serine levels under certain pathophysiological conditions contribute to neural dysfunction via NMDARs in the central nervous system. Entry of HIV-1 in the brain causes neuronal injury leading to cognitive, behavioral and motor impairments known as HIV-associated neurocognitive disorders (HAND). As HIV-1 does not infect neurons, neuronal injury is believed to be primarily mediated by an indirect mechanism,that is, HIV-1-infected and/or immune-activated macrophages and microglial cells release soluble molecules leading to neuronal injury or death. Among the soluble factors is D-serine. In this article we try to address recent progresses on the role D-serine might play in the pathogenesis of neurodegenerative disorders with a particular emphasis of the involvement of D-serine in HIV-1-associated neurotoxicity.
authors.affiliation: Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE 68198-5880, USA.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Xia
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
keywords: D-amino acids; D-serine; NMDA receptors; central nervous system; glycine site; neurodegeneration
references.citation: Nature. 1992 May 7;357(6373):70-4
references.pmid: 1374164
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3948-52
references.pmid: 7732010
references.citation: Neurology. 2007 Oct 30;69(18):1789-99
references.pmid: 17914061
references.citation: Science. 1969 Apr 11;164(3876):142-9
references.pmid: 5774186
references.citation: Pharmacol Rev. 1998 Dec;50(4):597-664
references.pmid: 9860805
references.citation: J Neuroimmune Pharmacol. 2006 Jun;1(2):138-51
references.pmid: 18040780
references.citation: Brain Res Bull. 2013 Apr;93:32-8
references.pmid: 23089362
references.citation: Brain Res. 1995 May 29;681(1-2):117-25
references.pmid: 7552268
references.citation: Nat Rev Neurosci. 2010 Oct;11(10):682-96
references.pmid: 20842175
references.citation: Neurochem Res. 2000 May;25(5):553-60
references.pmid: 10905615
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1340-5
references.pmid: 12552130
references.citation: Annu Rev Neurosci. 1990;13:171-82
references.pmid: 1970230
references.citation: Int Rev Neurobiol. 2007;82:57-71
references.pmid: 17678955
references.citation: N Engl J Med. 1994 Mar 3;330(9):613-22
references.pmid: 7905600
references.citation: Trends Pharmacol Sci. 1996 Oct;17(10):348-55
references.pmid: 8979769
references.citation: Neurol Clin. 2008 Aug;26(3):799-819, x
references.pmid: 18657727
references.citation: Neurosci Lett. 2006 Feb 20;394(3):163-7
references.pmid: 16298487
references.citation: Brain Res. 1999 Feb 20;819(1-2):65-74
references.pmid: 10082862
references.citation: J Biol Chem. 1994 Apr 15;269(15):10967-70
references.pmid: 8157620
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7589-94
references.pmid: 19380732
references.citation: Neurology. 1993 Nov;43(11):2245-52
references.pmid: 8232937
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7162-6
references.pmid: 7638161
references.citation: Nat Rev Neurosci. 2010 Apr;11(4):227-38
references.pmid: 20300101
references.citation: J Neurosci. 1995 Oct;15(10):6509-20
references.pmid: 7472413
references.citation: Glia. 2006 Mar;53(4):401-11
references.pmid: 16342169
references.citation: Trends Neurosci. 2005 May;28(5):229-38
references.pmid: 15866197
references.citation: Nature. 2002 Feb 14;415(6873):793-8
references.pmid: 11823786
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2950-5
references.pmid: 17293453
references.citation: J Biosci. 2005 Jun;30(3):391-405
references.pmid: 16052077
references.citation: J Neuroimmune Pharmacol. 2010 Sep;5(3):294-309
references.pmid: 20396973
references.citation: J Neurochem. 1993 Oct;61(4):1561-4
references.pmid: 8397299
references.citation: Microbes Infect. 2011 May;13(5):419-25
references.pmid: 21262373
references.citation: Nat Neurosci. 2001 Jul;4(7):702-10
references.pmid: 11426226
references.citation: Eur J Pharmacol. 2003 Aug 1;474(1):53-62
references.pmid: 12909195
references.citation: J Neurosci. 2006 Apr 26;26(17):4559-66
references.pmid: 16641235
references.citation: EMBO J. 2007 Sep 19;26(18):4149-59
references.pmid: 17762863
references.citation: Amino Acids. 2012 Nov;43(5):1851-60
references.pmid: 22886346
references.citation: Nature. 2005 Dec 22;438(7071):1167-71
references.pmid: 16372012
references.citation: Mol Genet Metab. 2005 Jul;85(3):168-80
references.pmid: 15979028
references.citation: Curr Opin Chem Biol. 1999 Aug;3(4):441-7
references.pmid: 10419857
references.citation: Brain Res. 2011 Jul 15;1401:104-17
references.pmid: 21676380
references.citation: Mol Neurobiol. 2007 Oct;36(2):152-64
references.pmid: 17952659
references.citation: Cell Death Differ. 2005 Aug;12 Suppl 1:878-92
references.pmid: 15832177
references.citation: Prog Neurobiol. 2005 Jun;76(2):77-98
references.pmid: 16081203
references.citation: Science. 1969 May 9;164(3880):719-21
references.pmid: 5778021
references.citation: Neurosci Lett. 2006 Jan 9;392(1-2):75-8
references.pmid: 16182447
references.citation: Neuroscience. 1998 Mar;83(2):449-58
references.pmid: 9460753
references.citation: J Neuroimmune Pharmacol. 2009 Dec;4(4):430-47
references.pmid: 19768553
references.citation: Curr Alzheimer Res. 2011 Aug;8(5):552-62
references.pmid: 21244351
references.citation: FEBS Lett. 1992 Jan 13;296(1):33-6
references.pmid: 1730289
references.citation: J Comp Neurol. 2002 Sep 2;450(4):303-17
references.pmid: 12209845
references.citation: Curr Opin Neurobiol. 2001 Jun;11(3):327-35
references.pmid: 11399431
references.citation: Bioconjug Chem. 2004 Jul-Aug;15(4):790-8
references.pmid: 15264866
references.citation: Annu Rev Pharmacol Toxicol. 2003;43:335-58
references.pmid: 12540744
references.citation: Neuroscience. 2009 Jan 12;158(1):275-83
references.pmid: 18358625
references.citation: Pharmacol Ther. 1999 Mar;81(3):163-221
references.pmid: 10334661
references.citation: Ann N Y Acad Sci. 2004 Dec;1035:133-46
references.pmid: 15681805
references.citation: J Neurochem. 1993 Feb;60(2):783-6
references.pmid: 8419554
references.citation: Curr Alzheimer Res. 2007 Jul;4(3):243-51
references.pmid: 17627481
references.citation: Eur J Clin Invest. 2002 Aug;32(8):619-27
references.pmid: 12190962
references.citation: Nature. 2001 Apr 19;410(6831):988-94
references.pmid: 11309629
references.citation: Nature. 2005 Nov 10;438(7065):185-92
references.pmid: 16281028
references.citation: Annu Rev Neurosci. 1994;17:31-108
references.pmid: 8210177
references.citation: J Neurosci. 2009 Jul 1;29(26):8429-37
references.pmid: 19571133
references.citation: J Neurovirol. 2003 Apr;9(2):205-21
references.pmid: 12707851
references.citation: Neurochem Int. 2012 Jun;60(8):837-45
references.pmid: 22465696
references.citation: Science. 1992 May 22;256(5060):1217-21
references.pmid: 1350383
references.citation: FEBS J. 2008 Jul;275(14):3514-26
references.pmid: 18564180
references.citation: J Immunol. 2000 Apr 15;164(8):4265-70
references.pmid: 10754324
references.citation: Nature. 1998 May 28;393(6683):377-81
references.pmid: 9620802
references.citation: J Biol Chem. 2006 May 19;281(20):14151-62
references.pmid: 16551623
references.citation: J Neurosci. 1995 Oct;15(10):6498-508
references.pmid: 7472412
references.citation: Curr HIV Res. 2006 Jul;4(3):307-18
references.pmid: 16842083
references.citation: Retrovirology. 2006 May 19;3:28
references.pmid: 16712719
references.citation: J Chem Neuroanat. 2005 May;29(3):157-72
references.pmid: 15820618
references.citation: Neuropharmacology. 2012 Mar;62(3):1484-503
references.pmid: 21295046
references.citation: J Neurochem. 1997 Sep;69(3):1286-90
references.pmid: 9282954
references.citation: Nature. 1998 Jan 15;391(6664):281-5
references.pmid: 9440691
references.citation: Cell Death Differ. 2005 Aug;12 Suppl 1:893-904
references.pmid: 15761472
references.citation: Rev Med Virol. 2012 Jan;22(1):33-45
references.pmid: 21990255
references.citation: Curr Opin Struct Biol. 1995 Dec;5(6):830-6
references.pmid: 8749373
references.citation: Chem Biodivers. 2010 Jun;7(6):1531-48
references.pmid: 20564568
references.citation: J Neurosci. 1999 May 15;19(10):4180-8
references.pmid: 10234045
references.citation: Brain Res Bull. 1995;38(2):181-3
references.pmid: 7583345
references.citation: J Neurosci. 2003 Jun 15;23(12):4958-66
references.pmid: 12832518
references.citation: Neuroscience. 1995 Jun;66(3):635-43
references.pmid: 7644027