PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, 21100 Varese, Italy.
Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Int J Mol Sci. 2021 Apr 6;22(7):3781. doi: 10.3390/ijms22073781.
Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.
帕金森病（PD）是一种由中脑多巴胺能神经元丧失引起的神经退行性疾病。PD 的临床特征为多种运动和非运动症状，治疗依赖于多巴胺能替代疗法。除了常见的病理标志外，PD 患者在临床进展和药物治疗反应方面可能存在差异，部分受遗传因素影响。尽管对多巴胺能受体（DR）的遗传变异性有广泛的了解，但很少有研究探讨其作为 PD 患者临床异质性的可能影响因素的相关性。在这篇综述中，我们总结了有关 DR 遗传多态性作为 PD 发生、进展和治疗反应的可能决定因素的现有证据。此外，我们还研究了 DR 在调节外周免疫中的作用，因为外周免疫系统在 PD 病理生理学中的作用正在不断显现。更好地了解所有这些方面是朝着开发针对 PD 的精确和个体化疾病修饰治疗方法迈出的重要一步。
