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

International Journal of Physiology, Pathophysiology and Pharmacology

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