Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Int J Mol Sci. 2017 Sep 22;18(10):2044. doi: 10.3390/ijms18102044.
Schizophrenia is a major psychiatric disorder that afflicts about 1% of the world's population, falling into the top 10 medical disorders causing disability. Existing therapeutic strategies have had limited success on cognitive impairment and long-term disability and are burdened by side effects. Although new antipsychotic medications have been launched in the past decades, there has been a general lack of significant innovation. This lack of significant progress in the pharmacotherapy of schizophrenia is a reflection of the complexity and heterogeneity of the disease. To date, many susceptibility genes have been identified to be associated with schizophrenia. gene, which encodes dysbindin-1, has been linked to schizophrenia in multiple populations. Studies on genetic variations show that modulate prefrontal brain functions and psychiatric phenotypes. Dysbindin-1 is enriched in the dorsolateral prefrontal cortex and hippocampus, while postmortem brain studies of individuals with schizophrenia show decreased levels of dysbindin-1 mRNA and protein in these brain regions. These studies proposed a strong connection between dysbindin-1 function and the pathogenesis of disease. Dysbindin-1 protein was localized at both pre- and post-synaptic sites, where it regulates neurotransmitter release and receptors signaling. Moreover, dysbindin-1 has also been found to be involved in neuronal development. Reduced expression levels of dysbindin-1 mRNA and protein appear to be common in dysfunctional brain areas of schizophrenic patients. The present review addresses our current knowledge of dysbindin-1 with emphasis on its potential role in the schizophrenia pathology. We propose that dysbindin-1 and its signaling pathways may constitute potential therapeutic targets in the therapy of schizophrenia.
精神分裂症是一种主要的精神疾病，影响着全球约 1%的人口，位列导致残疾的前 10 大医学疾病之列。现有的治疗策略在认知障碍和长期残疾方面收效甚微，且存在副作用。尽管过去几十年推出了新的抗精神病药物，但总体上缺乏重大创新。精神分裂症药物治疗缺乏显著进展反映了该疾病的复杂性和异质性。迄今为止，已经确定了许多与精神分裂症相关的易感基因。 基因，编码二联蛋白-1，已在多个群体中与精神分裂症相关。遗传变异研究表明，它可以调节前额叶脑功能和精神表型。二联蛋白-1在背外侧前额叶皮层和海马体中富集，而精神分裂症个体的死后大脑研究显示这些脑区中二联蛋白-1 mRNA 和蛋白水平降低。这些研究提出了二联蛋白-1功能与疾病发病机制之间的紧密联系。二联蛋白-1蛋白位于突触前和突触后部位，调节神经递质释放和受体信号转导。此外，二联蛋白-1还参与神经元发育。精神分裂症患者功能失调的脑区中二联蛋白-1 mRNA 和蛋白的表达水平降低似乎很常见。本综述介绍了我们目前对二联蛋白-1的认识，重点介绍了它在精神分裂症发病机制中的潜在作用。我们提出，二联蛋白-1及其信号通路可能成为精神分裂症治疗的潜在治疗靶点。
