期刊
CURRENT MEDICINAL CHEMISTRY
卷 19, 期 8, 页码 1119-1134出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986712799320574
关键词
Dimerisation; drug discovery; GPCR; heteromers; receptor crosstalk; receptor signaling; Parkinson disease; schizophrenia
资金
- La MARATO de TV3 Foundation [091010]
- Ministerio de Educacion y Ciencia [SAF2009-13609-C04-04]
Crosstalk between G protein-coupled receptors (GPCRs) is one of the key mechanisms used by the cell for integrating multiple signaling pathways. Functional crosstalk at the level of signaling pathways was initially thought to regulate receptor function. Importantly, the existence of GPCR heteromers demonstrates that direct physical interactions between GPCRs could also be behind the crosstalk phenomenon. Neurological disorders such as Parkinson's disease (PD) and schizophrenia have been linked to a dysfunctional communication between certain GPCRs. In this review, we discuss functional and physical crosstalk of the main GPCR families involved in the aforementioned disorders. In addition, we analyze the available structural information on physical crosstalk and highlight some strategies in drug discovery based on these crosstalk mechanisms.
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