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The involvement of DARPP-32 in the pathophysiology of schizophrenia
Wang, Haitao1,2; Farhan, Mohd1; Xu, Jiangping2; Lazarovici, Philip3; Zheng, Wenhua1
2017-08-08
Source PublicationONCOTARGET
ISSN1949-2553
Volume8Issue:32Pages:53791-53803
Abstract

Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control. Accumulating evidences has indicated the involvement of DARPP-32 in the development of schizophrenia; i. DARPP-32 phosphorylation is regulated by several neurotransmitters, including dopamine and glutamate, neurotransmitters implicated in schizophrenia pathogenesis; ii. decrease of both total and phosphorylated DARPP-32 in the prefrontal cortex are observed in schizophrenic animal models; iii. postmortem brain studies indicated decreased expression of DARPP-32 protein in the superior temporal gyrus and dorsolateral prefrontal cortex in patients with schizophrenia; iv. DARPP-32 phosphorylation is increased upon therapy with antipsychotic drugs, such as haloperidol and risperidone which improve behavioral performance in experimental animal models and patients; v. Genetic analysis of the gene coding for DARPP-32 propose an association with schizophrenia. Cumulatively, these findings implicate DARPP-32 protein in schizophrenia and propose it as a potential therapeutic target. Here, we summarize the possible roles of DARPP-32 during the development of schizophrenia and make some recommendations for future research. We propose that DARPP-32 and its interacting proteins may serve as potential therapeutic targets in the treatment of schizophrenia.

KeywordSchizophrenia Darpp-32 Dopamine Camp Glutamate
DOI10.18632/oncotarget.17339
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000407124100144
PublisherIMPACT JOURNALS LLC
The Source to ArticleWOS
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Cited Times [WOS]:10   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Faculty of Health Sciences, University of Macau, Taipa, Macau, China
2.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
3.School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Wang, Haitao,Farhan, Mohd,Xu, Jiangping,et al. The involvement of DARPP-32 in the pathophysiology of schizophrenia[J]. ONCOTARGET,2017,8(32):53791-53803.
APA Wang, Haitao,Farhan, Mohd,Xu, Jiangping,Lazarovici, Philip,&Zheng, Wenhua.(2017).The involvement of DARPP-32 in the pathophysiology of schizophrenia.ONCOTARGET,8(32),53791-53803.
MLA Wang, Haitao,et al."The involvement of DARPP-32 in the pathophysiology of schizophrenia".ONCOTARGET 8.32(2017):53791-53803.
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