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Another important PD hallmark, Lewy body (LB) pathology, which appears in 77% to 95% PD patients accordingtodifferentstudies[ 3,4],iscommonly illustrated by phosphorylatedserine129 -synuclein (PSer129 S) immunostaining. BRIEFCOMMUNICATION National Science Review 8:nwaa292,2021 doi:10.1093/nsr/nwaa292 Advanceaccesspublication10December2020 NEUROSCIENCE A cynomolgus monkey with naturally occurring Parkinson's disease HaoLi 1,†,Ling-YanSu 1,†,LixinYang 2,11,†,MinLi 2,†,QianjinLiu 1,3,†,ZhenhuiLi 1,3,†,YanHu 2,3, HongweiLi 1,ShihaoWu 1,5,WenchaoWang 1,YingzhouHu 1,ZhengboWang 1,JoshuaD.Rizak 1, BaihuiHuang 1,MinXu 1,3,JingWu 1,Long-BaoLv 6,ChristophW.Turck 1,7,*,YongYin 8,*, Yong-GangYao 1,3,4,6,9,*,BingSu 2,6,10,* andXintianHu 1,4,6,* Evidence for the existence of monkeys with spontaneous Parkinson's disease (PD) has been lacking. Collectively, four lines of evidence, including typical PD clinical symptoms, pharmacological responses, pathology hallmarks and genetic mutations, stronglysuggestedthatwehadidentified acynomolgusmonkeywithspontaneous PD. (C) The total PD score of the monkey was reduced significantly from 17.7 to 9.3 after a classic PD drug L-dopa treatment, indicating a significant positive response to the treatment. [Extracted from the article]

Phosphorylation of α-synuclein at serine 129 (P-Ser 129 α-syn) is involved in the pathogenesis of Parkinson’s disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quantitative relation of P-Ser 129 α-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brain areas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing a modeling-recovery-remodeling strategy. Compared to age-matched controls, the MPTP-treated monkeys showed significantly reduced tyrosine hydroxylase (TH)-positive neurons and increased P-Ser 129 α-syn-positive aggregations in the SN. Double-labeling Immunofluorescence found some TH-positive neurons to be co-localized with P-Ser129 α-syn in the SN, suggesting the inverse correlation between P-Ser 129 α-syn aggregations and dopaminergic cell loss in the SN may represent an interactive association related to the progression of the PD symptoms in the model. P-Ser 129 α-syn aggregations or LB-like pathology was also found in the midbrain and the neocortex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cells surrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 α-syn negative. The findings of LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest that the modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investigations into the pathogenesis of PD and potential therapeutic development. [ABSTRACT FROM AUTHOR]