Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, 92215 Lodz, Poland.
Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
Cells. 2021 May 17;10(5):1228. doi: 10.3390/cells10051228.
Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.
精神分裂症是一种常见的使人虚弱的疾病，其特征是持续或反复发作的精神病。尽管这种精神疾病的分子机制仍不完全清楚，但越来越多的临床、药理学和遗传学证据表明，G 蛋白偶联受体 (GPCRs) 在疾病的发展、进展和治疗中起着关键作用。GPCRs 是抗精神病药物最常见的靶点，这一关键作用进一步得到了强调。GPCRs 的激活通过几个下游途径引发缓慢的突触传递，其中许多途径涉及细胞内钙动员。涉及 GPCR 作用的神经递质系统的功能障碍在前额和边缘相关区域可能是导致包括阳性和阴性精神分裂症症状的整个谱的复杂情况的基础。因此，我们对 GPCR 在控制大脑认知功能中的作用的理解的进展有望为选择性药物开发开辟新途径。在本文中，我们综述和综合了最近关于神经递质-GPCRs 信号对精神分裂症症状的贡献的数据。
