Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, Portugal.
Curr Neuropharmacol. 2022;20(11):2081-2141. doi: 10.2174/1570159X20666220327221830.
Neurodegenerative diseases affect over 30 million people worldwide with an ascending trend. Most individuals suffering from these irreversible brain damages belong to the elderly population, with onset between 50 and 60 years. Although the pathophysiology of such diseases is partially known, it remains unclear upon which point a disease turns degenerative. Moreover, current therapeutics can treat some of the symptoms but often have severe side effects and become less effective in long-term treatment. For many neurodegenerative diseases, the involvement of G proteincoupled receptors (GPCRs), which are key players of neuronal transmission and plasticity, has become clearer and holds great promise in elucidating their biological mechanism. With this review, we introduce and summarize class A and class C GPCRs, known to form heterodimers or oligomers to increase their signalling repertoire. Additionally, the examples discussed here were shown to display relevant alterations in brain signalling and had already been associated with the pathophysiology of certain neurodegenerative diseases. Lastly, we classified the heterodimers into two categories of crosstalk, positive or negative, for which there is known evidence.
神经退行性疾病影响全球超过 3000 万人,且呈上升趋势。大多数患有这些不可逆转的大脑损伤的人属于老年人群体,发病年龄在 50 至 60 岁之间。尽管这些疾病的病理生理学部分已知,但仍不清楚疾病在何时开始退行性变化。此外,目前的治疗方法可以治疗一些症状,但往往有严重的副作用,并且在长期治疗中效果会降低。对于许多神经退行性疾病,G 蛋白偶联受体(GPCRs)的参与变得更加清晰,GPCRs 是神经元传递和可塑性的关键参与者,它们在阐明其生物学机制方面具有很大的潜力。在这篇综述中,我们介绍并总结了 A 类和 C 类 GPCRs,已知它们可以形成异源二聚体或寡聚体来增加其信号转导谱。此外,这里讨论的例子显示出大脑信号的相关改变,并且已经与某些神经退行性疾病的病理生理学相关联。最后,我们将异源二聚体分为两种类型的串扰,即已知存在证据的正或负串扰。