| The neurobiology of D-amino acid oxidase and its involvement in schizophrenia. | |
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MedLine Citation:
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PMID: 19786963 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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D-amino acid oxidase (DAO) is a flavoenzyme that metabolizes certain D-amino acids, notably the endogenous N-methyl D-aspartate receptor (NMDAR) co-agonist, D-serine. As such, it has the potential to modulate the function of NMDAR and to contribute to the widely hypothesized involvement of NMDAR signalling in schizophrenia. Three lines of evidence now provide support for this possibility: DAO shows genetic associations with the disorder in several, although not all, studies; the expression and activity of DAO are increased in schizophrenia; and DAO inactivation in rodents produces behavioural and biochemical effects, suggestive of potential therapeutic benefits. However, several key issues remain unclear. These include the regional, cellular and subcellular localization of DAO, the physiological importance of DAO and its substrates other than D-serine, as well as the causes and consequences of elevated DAO in schizophrenia. Herein, we critically review the neurobiology of DAO, its involvement in schizophrenia, and the therapeutic value of DAO inhibition. This review also highlights issues that have a broader relevance beyond DAO itself: how should we weigh up convergent and cumulatively impressive, but individually inconclusive, pieces of evidence regarding the role that a given gene may have in the aetiology, pathophysiology and pharmacotherapy of schizophrenia? |
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Authors:
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L Verrall; P W J Burnet; J F Betts; P J Harrison |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2009-09-29 |
Journal Detail:
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Title: Molecular psychiatry Volume: 15 ISSN: 1476-5578 ISO Abbreviation: Mol. Psychiatry Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-25 Completed Date: 2010-03-30 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 9607835 Medline TA: Mol Psychiatry Country: England |
Other Details:
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Languages: eng Pagination: 122-37 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / enzymology D-Amino-Acid Oxidase / genetics, metabolism* Genetic Predisposition to Disease* Genome-Wide Association Study Humans Models, Biological Neurobiology* Receptors, N-Methyl-D-Aspartate / genetics, metabolism Schizophrenia / enzymology*, genetics, pathology |
| Grant Support | |
ID/Acronym/Agency:
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G0500180(73693)//Medical Research Council; G0801352(87861)//Medical Research Council; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Receptors, N-Methyl-D-Aspartate; EC 1.4.3.3/D-Amino-Acid Oxidase |
| Comments/Corrections | |
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