Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions.
Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions.
复制标题
DOI：
10.3390/ijms18010135
复制
发表时间：
2017-01-12
影响因子：
5.6
通讯作者：
de Bartolomeis A
中科院分区：
文献类型：
--
作者：
Tomasetti C;Iasevoli F;Buonaguro EF;De Berardis D;Fornaro M;Fiengo AL;Martinotti G;Orsolini L;Valchera A;Di Giannantonio M;de Bartolomeis A
多巴胺-谷氨酸相互作用功能障碍已被认为是主要精神障碍的病理生理关键决定因素，尤其是精神分裂症和情绪障碍。在大多数情况下，多巴胺和谷氨酸信号通路之间的突触相互作用参与突触后密度，这是一种位于谷氨酸能兴奋性突触膜下的特殊超微结构。多种蛋白质，在接头、调节、效应和支架的作用下组成突触后密度网络。它们形成了结构和功能的十字路口，从膜受体开始的多种信号被接收、加工、整合并传递到适当的核目标。此外，属于不同受体的转导通路可能通过突触后密度分子在功能上相互连接。一些研究表明，精神药理学药物可能会影响突触后基因和蛋白质的表达和功能，这取决于每种化合物的特殊受体谱。因此，通过突触后网络调节，这些药物可能诱导多巴胺-谷氨酸突触重塑，这是其长期生理作用的基础。在这篇综述中，我们将讨论突触后蛋白在多巴胺-谷氨酸信号整合中的作用，以及临床应用的不同精神药物对突触后重塑的特殊影响，从而试图指出未来可能的“突触为基础”的精神治疗策略的分子靶点。
Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of “synapse-based” psychiatric therapeutic strategies.