Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons. GPR37 also constitutes a core structure of Lewy bodies, demonstrating a more general involvement in PD pathology. However, if folded and matured properly, GPR37 seems to be neuroprotective. Moreover, GPR37 modulates functionality of the dopamine transporter and the dopamine D2 receptor and stimulates dopamine neurotransmission. Here we review the multiple roles of GPR37 with relevance to potential disease modification and symptomatic therapies of PD and highlight unsolved issues in this field.

由于蛋白质功能所需的构象柔韧性是以结构稳定性为代价的，因此许多蛋白质，包括G蛋白偶联受体（GPCR），始终处于错误折叠和聚集的风险中。在这方面，GPR37（也称为PAEL-R和ETBR-LP-1）起着重要作用，尤其是在帕金森氏病（PD）方面。GPR37是Parkin的底物，在常染色体隐性少年帕金森病中异常蓄积，导致内质网应激和多巴胺能神经元死亡。GPR37还构成了路易小体的核心结构，表明其更广泛地参与了PD病理学的研究。但是，如果折叠并正确成熟，GPR37似乎具有神经保护作用。而且，GPR37调节多巴胺转运蛋白和多巴胺D2受体的功能，并刺激多巴胺的神经传递。在这里，我们回顾了GPR37与PD的潜在疾病改良和对症治疗有关的多种作用，并着重指出了该领域尚未解决的问题。