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Int J Physiol Pathophysiol Pharmacol 2013;5(3):137-147

Review Article
Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible
involvement of D-serine

Jianxun Xia, Huangui Xiong

Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center,
Omaha, NE 68198-5880, USA

Received May 1, 2013; Accepted July 28, 2013; Epub September 10, 2013; Published September 15, 2013

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. (IJPPP1305001).

Keywords: D-serine, D-amino acids, NMDA receptors, glycine site, neurodegeneration, central nervous system

Address correspondence to: Dr. Huangui Xiong, Neurophysiology Laboratory, Department of Pharmacology and Experimental
Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. Tel: 402-559-5140; Fax: 402-559-3744; E-mail:
hxiong@unmc.edu