Wang Mengya, Liu Huayuan, Ma Zegang
Department of Physiology, School of Basic Medicine, Institute of Brain Science and Disorders, Qingdao University, Qingdao, China.
Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.
Front Cell Neurosci. 2022 Feb 21;16:832854. doi: 10.3389/fncel.2022.832854. eCollection 2022.
Parkinson's disease (PD) is a neurodegenerative disease usually caused by neuroinflammation, oxidative stress and other etiologies. Recent studies have found that the cannabinoid system present in the basal ganglia has a strong influence on the progression of PD. Altering the cannabinoid receptor activation status by modulating endogenous cannabinoid (eCB) levels can exert an anti-movement disorder effect. Therefore, the development of drugs that modulate the endocannabinoid system may be a novel strategy for the treatment of PD. However, eCB regulation is complex, with diverse cannabinoid receptor functions and the presence of dopaminergic, glutamatergic, and γ-aminobutyric signals interacting with cannabinoid signaling in the basal ganglia region. Therefore, the study of eCB is challenging. Here, we have described the function of the cannabinoid system in the basal ganglia and its association with PD in three parts (eCBs, cannabinoid receptors, and factors regulating the cannabinoid metabolism) and summarized the mechanisms of action related to the cannabinoid analogs currently aimed at treating PD. The shortcomings identified from previous studies and the directions that should be explored in the future will provide insights into new approaches and ideas for the future development of cannabinoid-based drugs and the treatment of PD.
帕金森病（PD）是一种通常由神经炎症、氧化应激和其他病因引起的神经退行性疾病。最近的研究发现，基底神经节中存在的大麻素系统对PD的进展有很大影响。通过调节内源性大麻素（eCB）水平来改变大麻素受体的激活状态，可以发挥抗运动障碍作用。因此，开发调节内源性大麻素系统的药物可能是治疗PD的一种新策略。然而，eCB的调节很复杂，在基底神经节区域存在多种大麻素受体功能以及多巴胺能、谷氨酸能和γ-氨基丁酸信号与大麻素信号相互作用。因此，对eCB的研究具有挑战性。在此，我们从三个部分（eCB、大麻素受体和调节大麻素代谢的因素）描述了基底神经节中大麻素系统的功能及其与PD的关联，并总结了目前旨在治疗PD的大麻素类似物的作用机制。从以往研究中发现的不足以及未来应探索的方向，将为基于大麻素的药物未来开发和PD治疗的新方法及新思路提供见解。
