Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Science, Smętna Street 12, 31-343 Kraków, Poland.
Department of Physical Biochemistry, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Int J Mol Sci. 2024 Mar 7;25(6):3089. doi: 10.3390/ijms25063089.
Numerous studies highlight the therapeutic potential of G protein-coupled receptor (GPCR) heterodimers, emphasizing their significance in various pathological contexts. Despite extensive basic research and promising outcomes in animal models, the translation of GPCR heterodimer-targeting drugs into clinical use remains limited. The complexities of in vivo conditions, particularly within thecomplex central nervous system, pose challenges in fully replicating physiological environments, hindering clinical success. This review discusses examples of the most studied heterodimers, their involvement in nervous system pathology, and the available data on their potential ligands. In addition, this review highlights the intricate interplay between lipids and GPCRs as a potential key factor in understanding the complexity of cell signaling. The multifaceted role of lipids in modulating the dynamics of GPCR dimerization is explored, shedding light on the elaborate molecular mechanisms governing these interactions.
大量研究强调了 G 蛋白偶联受体 (GPCR) 异源二聚体的治疗潜力,凸显了它们在各种病理情况下的重要性。尽管在基础研究方面取得了广泛进展,并在动物模型中取得了有前景的结果,但将针对 GPCR 异源二聚体的药物转化为临床应用仍然受到限制。体内条件的复杂性,特别是在复杂的中枢神经系统中,使得在生理环境中完全复制变得具有挑战性,从而阻碍了临床的成功。本文综述了研究最多的异源二聚体的例子,它们在神经系统病理学中的作用,以及它们潜在配体的现有数据。此外,本文还强调了脂质与 GPCR 之间的复杂相互作用,这可能是理解细胞信号转导复杂性的关键因素。本文探讨了脂质在调节 GPCR 二聚化动力学中的多方面作用,揭示了调控这些相互作用的精细分子机制。