International Journal of Physiology, Pathophysiology and Pharmacology | |
Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine | |
Huangui Xiong1  Jianxun Xia1  | |
[1] Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA | |
关键词: D-serine; D-amino acids; NMDA receptors; glycine site; neurodegeneration; central nervous system; | |
DOI : | |
学科分类:生理学与病理学 | |
来源: e-Century Publishing Corporation | |
【 摘 要 】
AuniquefeatureofN-methyl-D-aspartatereceptors(NMDARs)thatdistinguishesthemfromotherionicreceptorsisthattheiractivationrequiresmorethanoneagonisttobindsimultaneouslytodistinctbindingsitesonthereceptor.D-serine,aco-agonistbindingtotheglycinesiteofNMDARs,hasbeenimplicatedinseveralNMDAR-dependentphysiologicalprocesses,andalteredD-serinelevelsundercertainpathophysiologicalconditionscontributetoneuraldysfunctionviaNMDARsinthecentralnervoussystem.EntryofHIV-1inthebraincausesneuronalinjuryleadingtocognitive,behavioralandmotorimpairmentsknownasHIV-associatedneurocognitivedisorders(HAND).AsHIV-1doesnotinfectneurons,neuronalinjuryisbelievedtobeprimarilymediatedbyanindirectmechanism,thatis,HIV-1-infectedand/orimmune-activatedmacrophagesandmicroglialcellsreleasesolublemoleculesleadingtoneuronalinjuryordeath.AmongthesolublefactorsisD-serine.InthisarticlewetrytoaddressrecentprogressesontheroleD-serinemightplayinthepathogenesisofneurodegenerativedisorderswithaparticularemphasisoftheinvolvementofD-serineinHIV-1-associatedneurotoxicity.(IJPPP1305001).
【 授权许可】
Unknown
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