We recently identified a cynomolgus monkey with naturally occurring Parkinson's disease (PD), indicating that PD may not be a uniquely human disease (Li et al, 2020). In our previous study, four lines of evidence, including typical PD clinical symptoms, pharmacological responses, pathological hallmarks, and genetic mutations, strongly supported the identification of a monkey with spontaneous PD (Figure 1). To the best of our knowledge, this is the first reported case of naturally developed PD in animals. This suggests that PD is not a disease restricted to humans, with its existence in a non-human primate providing a novel evolutionary angle for understanding PD. As a close relative to humans (Buffalo et al, 2019; Phillips et al, 2014; Yan et al, 2011), this rare case of PD in another primate species provides solid evidence that monkeys are ideal candidates for the development of a genuine "animal version of PD", with conserved etiology and pathogenesis (Li et al, 2020). Furthermore, it allows us to compare similarities and differences in PD development between species and to understand PD pathogenesis from an evolutionary point of view.
我们发现了首例自发罹患帕金森病的食蟹猴（Li et al, 2020），其临床运动症状典型，包括运动迟缓、姿势异常与静止性震颤等；经典药物治疗的结果类似帕金森病患者的临床表现；组织病理学研究表明中脑黑质多巴胺能神经元的大量丢失（~70%），伴随胞内磷酸化alpha-synuclein的聚集（经典的路易小体早期病理），以及黑质出现路易突起与胶质细胞的增生和激活。基于此，该例自发罹患帕金森病的食蟹猴是非常经典的帕金森病案例，几乎具备帕金森病患者所有的核心表型。遗传分析显示此猴的LRRK2与ATP13A2基因出现了罕见的错义突变。该研究表明帕金森病的发生机制在人类出现以前就产生了，它不是一个人类特有的疾病。因此，利用猴子作为生物医学模型来研究帕金森病是非常可靠的。此猴发病可能与LRRK2突变相关，确切的发病机制需进一步实验证明。综上所述，帕金森病不是人类专属的疾病，利用猴子建立帕金森病模型具有坚实的生物学基础，而LRRK2可作为一个潜在的靶标用来建立转基因帕金森病猴模型。.
Keywords: Clinical symptoms; Naturally occurring model; Non-human primates; Parkinson’s disease; Pathogenesis; Pathological hallmarks.