Background: Insulin resistance (IR) has emerged as a key player in the pathogenesis of cognitive impairment in Parkinson's disease (PD). This study aims to systematically compare glucolipotoxicity-based (TyG, AIP) versus adiposity-driven (TyG-BMI, METS-IR) IR indices for their associations with PD dementia and to develop a clinically applicable nomogram using an interpretable machine learning framework. Methods: This cross-sectional study analyzed 251 PD patients: 42 with normal cognition, 160 with mild cognitive impairment (PD-MCI) and 49 with dementia (PDD). Logistic and linear regression examined associations between IR indices and cognitive impairment across different domains. Six machine learning models were compared for dementia classification, with the optimal model interpreted using SHapley Additive exPlanations (SHAP) to construct a nomogram. Results: Each standard deviation increase in TyG and AIP was linked to 79% (OR 1.79, 95%CI 1.04-3.07) and 75% (OR 1.75, 95%CI 1.05-2.91) higher risk of PDD, respectively, but not PD-MCI. In contrast, TyG-BMI and METS-IR showed no significant associations with either condition. TyG showed linear negative correlations with memory and orientation, and inverted U-shaped associations with visuospatial function and attention. AIP exhibited linear negative correlation with memory. The logistic regression model achieved the highest performance (AUC of 0.759) among six machine learning models. Crucially, SHAP analysis visually quantified TyG as a top modifiable predictor, facilitating the construction of an interpretable clinical nomogram. Conclusions: Glucolipotoxicity-based indices (TyG, AIP), unlike BMI-dependent markers (TyG-BMI, METS-IR), are robustly linked to PD dementia through domain-specific linear or nonlinear patterns. This suggests metabolic dysregulation predicts risk independent of weight loss. Furthermore, integrating SHAP-based interpretability transforms complex algorithms into a transparent, actionable tool for early risk stratification.

Previous studies have shown that alterations in the gut microbiota and its derived metabolites, branched-chain amino acids (BCAAs), are correlated with T-cell-associated immune imbalance and Parkinson’s disease (PD). However, the associations among BCAAs, gastrointestinal dysfunction and T-cell-related gut inflammation remain unclear. This study showed that the constipation symptoms in the PD mice persisted after chronic MPTP treatment. An imbalance in the CD4+ T-cell subtypes was observed in the colonic lamina propria (cLP), mesenteric lymph nodes (mLNs), and spleen. Metagenomic and metabolomic analyses showed that microbial dysbiosis promoted BCAA degradation rather than biosynthesis, and reduced BCAA levels were confirmed in the serum. BCAA supplementation alleviated constipation symptoms and increased Th1 and Th17 cell infiltration in the cLP, mLNs and spleen were significantly attenuated after BCAA treatment. This study highlights the therapeutic value of BCAAs in mitigating gut immune inflammation-associated constipation symptoms in PD.

Interleukin-33 (IL-33) regulates immune responses in central nervous system diseases. This study investigates the effect of IL-33 on astrocyte phenotypic transformation in Parkinson’s disease (PD). The associations of IL-33, soluble growth-stimulating expression gene 2 (sST2), with PD severity and clinical symptoms were examined. IL-33 supplementation and knockdown were applied in vivo and in vitro to assess IL-33’s impact on neuron loss, astrocyte polarization, and inflammation. Transcriptome sequencing was conducted to identify hub genes and pathways regulated by IL-33 in astrocytes, with validated in primary astrocytes. Plasma sST2 levels were elevated in PD patients and correlated with PD severity, while IL-33 decreased with disease progression. In PD models, IL-33 supplementation improved PD-like symptoms and A2 astrocyte polarization. Conversely, IL-33 knockdown worsened PD-like symptoms and neurotoxic polarization. RNA-seq identified the PENK-ERK/MAPK pathway as the key regulator of IL-33-mediated astrocyte transformation. In conclusion, IL-33 plays a crucial role in regulating astrocytes in PD.

The pathogenicity of variants of uncertain significance in the LRRK2 gene remains underexplored. Investigating the LRRK2 variant spectrum in a large Chinese population cohort can provide deeper insights into its pathogenic mechanisms. This study examined the LRRK2 gene variants in 20,519 Chinese individuals, including 7,562 Parkinson’s disease (PD) patients, 3,077 Essential tremor (ET) patients, and 9880 healthy controls. We conducted a genetic analysis of low-frequency and common non-synonymous variants in the LRRK2 gene across the cohorts. A total of 287 low-frequency non-synonymous LRRK2 variants were identified in the PD and control cohorts. Among these, six reported pathogenic variants (p.R1325Q, p.R1441C, p.R1441H, p.V1447M, p.G2019S, p.I2020T) and three reported likely pathogenic variants (p.R1067Q, p.N1437D, p.R1728H) were enriched in PD cases, with a frequency of 0.71%. In contrast, only one pathogenic variant (p.R1325Q) and one likely pathogenic variant (p.R1067Q) were observed in healthy controls (0.11%), and the ET cohort exhibited similar variant distribution to controls (0.19%). Burden analysis and association analysis revealed novel likely pathogenic variants, including p.A312V, p.M968K, and p.R1320S as candidates. These novel variants were significantly more frequent in PD patients (0.79%) compared to healthy controls (0.20%) or ET patients (0.42%). Additionally, seven common missense variants of LRRK2 were identified, and significant associations with PD for p.A419V, p.R1628P, and p.G2385R were confirmed, but no common variants were linked to ET. This study provides the first comprehensive characterization of the LRRK2 variant spectrum in a large Chinese population, underscoring the pivotal role of LRRK2 in PD pathogenesis but not in ET. These findings advance the understanding of LRRK2 in neurodegenerative disorders and lay a foundation for personalized therapeutic strategies based on genetic profiling.

Interstitial lung disease (ILD) is a heterogeneous group of diseases characterized by inflammation and interstitial fibrosis of the pulmonary parenchyma. Alternative activation of macrophages can promote fibrosis through the secretion of TGF-β1 in ILD. However, the mechanisms regulating alternative macrophage activation and TGF-β1 expression in ILD patients remain unclear. We demonstrated that cadherin-26 (CDH26) expression is upregulated in ILD patients' lungs and inversely correlated with lung function. CDH26 is predominantly expressed in macrophages in bronchoalveolar lavage cells from ILD patients. In a mouse model of bleomycin-induced pulmonary fibrosis, we found that macrophage-specific Cdh26 deficiency significantly attenuated bleomycin-induced fibrosis, collagen deposition, alternative activation-associated (M2-like) macrophage polarization, and Tgf-β1 expression. In vivo and vitro experiments showed that Cdh26 deficiency was associated with suppression of the Ctnnb1-Stat3 signaling axis in macrophages. Our study delineates a novel CDH26-mediated signaling in lung fibrosis, and CDH26 may represent a potential therapeutic target for ILD.

The switch from oxidative phosphorylation to glycolysis is crucial for microglial activation. Recent studies highlight that histone lactylation promotes macrophage homeostatic gene expression via transcriptional regulation, but its role in microglia activation in Parkinson’s disease (PD) remains unclear. Here, we demonstrated that inhibiting glycolysis with 2-deoxy-d-glucose alleviates microgliosis, neuroinflammation and dopaminergic neurons damage by reducing lactate accumulation in PD mice. Notably, we observed a marked increase in histone lactylation, particularly H3K9 lactylation, in microglia in the substantia nigra of PD mice. Mechanistically, CUT&Tag and Chip-qPCR analyses revealed that H3K9 lactylation enriched at the SLC7A11promoter and activated its expression. Importantly, inhibiting SLC7A11 by sulfasalazine mitigated microglia-mediated neuroinflammation and improved motor function in PD mice. Moreover, we found that lactate-induce histone lactylation is dependent on P300/CBP. Collectively, our findings demonstrate that glycolysis-derived lactate promotes microglial activation via histone lactylation and provide a potential therapeutic strategy for PD.

OBJECTIVES:As extensively researched metabolites, short chain fatty acids (SCFAs) undergo significant alterations in individuals with Parkinson's disease (PD). This meta-analysis was conducted to (1) explore the relationship between SCFAs and PD, and (2) provide evidence for the metabolic mechanisms underlying PD pathogenesis. METHODS:A systematic search of four electronic databases (PubMed, Embase, Web of Science and Cochrane Library) was conducted up to February 29, 2024. The Agency of Healthcare Research and Quality (AHRQ) criteria were used for quality evaluation. Forest plots were used to display the results of the meta-analysis, and publication bias was assessed using funnel plots, Begg's tests and Egger's tests. Sensitivity analysis revealed heterogeneous sources among the included studies. RESULTS:A total of 9 independent studies were enrolled, including 485 PD patients and 338 controls. In this meta-analysis, we discovered that, in comparison to healthy controls, stool acetic (SMD: -0.80; 95% CI: -1.23, -0.37), butyric (SMD: -0.71; 95% CI: -1.19, -0.24) and propionic acids (SMD: -0.98; 95% CI: -1.57, -0.40) were decreased, while plasma butyric (SMD: 0.25; 95% CI: 0.05, 0.44), isobutyric (SMD: 0.35, 95% CI: 0.11, 0.59) and propionic acids (SMD: 0.37, 95% CI: 0.16, 0.58) were increased in PD patients. Other SCFAs were not significantly different between the two groups. CONCLUSIONS:The evidence from this meta-analysis demonstrates that the stool and plasma SCFAs of PD patients are distinct from those of the control group. This study highlights SCFAs' potential importance as novel interventional targets.

Parkinson’s disease (PD) is characterized by the aggregation of α-synuclein (α-syn) and the loss of dopaminergic (DA) neurons, with growing evidence suggesting a significant role of gut microbiota and their metabolites in the disease’s pathogenesis. This study explores the effects of short-chain fatty acids (SCFAs) on PD progression, focusing on the G protein–coupled receptor 43 (GPR43) and the NLRP3 signaling pathway in both in vitro and in vivo models. Employing the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model and SH-SY5Y cells with SCFAs-treated, this study investigated the impact of SCFAs on α-syn deposition, DA loss, and neuroinflammation. In vitro, supernatant from STC-1 cells was administered to SH-SY5Y cells, and the effects were assessed following the knockdown of NLRP3 or GPR43. In vivo, mice were treated with NLRP3 or GPR43 inhibitors after feeding with SCFAs, and the motor deficits, α-syn pathology, DA neuronal loss, and inflammatory responses were observed. SCFAs were found to exacerbate motor and gastrointestinal dysfunctions in PD models, intensifying α-syn pathology and neuroinflammation. The activation of the NLRP3 inflammasome through GPR43 emerged as a key pathological mechanism, with inhibition of these molecules mitigating the observed effects. Such interventions reduced α-syn accumulation, DA loss, and inflammatory responses, highlighting the pivotal role of the SCFA/GPR43-NLRP3 pathway in PD. The findings from this study elucidate a critical link between gut-derived metabolic changes and neuroinflammatory processes in PD via the SCFA/GPR43-NLRP3 pathway. Targeting this pathway offers a promising therapeutic strategy and enriches our understanding of the gut-brain axis’ role in PD progression.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein (α-syn) aggregation. Lipid metabolism dysfunction may contribute to PD progression. This study aims to identify lipid metabolism-related genes (LMGs) associated with PD using an integrative transcriptomic analysis of microarray and single-cell RNA sequencing (scRNA-seq) datasets from patients with PD and healthy controls. Differentially expressed genes (DEGs) related to lipid metabolism were identified, and key genes were further filtered using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. Four LMGs, AGPAT2, ASAH2, FA2H, and MECR were identified, with MECR being notably downregulated in both bulk and single-cell transcriptomic analyses of PD patients. This downregulation was further validated in α-syn PFF-induced PD models. Virtual screening and molecular simulations identified potential allosteric modulators of MECR, which may offer a pathway for future therapeutic exploration. This study highlights MECR as a critical gene link between lipid metabolism dysfunction and PD, suggesting the need for further investigation into its therapeutic implications.

Transcranial ultrasound (TCS) imaging can quantitatively measure third ventricle width (TVW) in Parkinson's (PD) patients, helping physicians detect cognitive dysfunction in PD patients as early as possible. However, the transmitted unified TVW measurement has problems such as low efficiency and unstable measurement. For this reason, this paper proposes an automatic TVW measurement for TCS images. Firstly, to solve the problem of third ventricle detection in the complex background of TCS images, the YOLO-TV improvement model is proposed to improve the detection accuracy. The YOLO-TV model introduces a multi-head attention mechanism in the feature extraction network to enhance the network to extract feature at different scales. Meanwhile, a depth separable path aggregation module is used to improve the channel sensitivity of the feature fusion. Secondly, to solve the problem of third ventricle segmentation measurement, a third ventricle segmentation algorithm based on local intensity features is proposed, which realizes automatic segmentation measurement of third ventricle by calculating the local intensity features of the region and localization of the multi-angle projection method. The detection accuracy of the YOLO-TV model in the validation set reaches 98.50%, and the average measurement deviation between the automatic measurement results of the method proposed in this paper and the manual measurement results of the doctors is 0.089 mm, and the correlation coefficient between the two is 0.9643, which indicates that the method can be used to accurately measure the width of third ventricle.

The coexistence of Parkinson's disease (PD) and myasthenia gravis (MG) is rare. When similar symptoms of both diseases overlap, it is challenging to make a concomitant diagnosis of PD and MG. The present study describes the case of a patient with concomitant PD and MG. In addition, a systematic literature review was conducted by searching PubMed and Embase for reports on all patients with concomitant PD and MG, which were then grouped and compared according to different preexisting diseases. Finally, a total of 47 cases of concomitant PD and MG (35 men; 12 women), including the present case, were analyzed. The median age of the patients at first diagnosis was 66.59 +/- 9.91 years. The interval between the two diseases varied from 2 months to 22 years. Based on the sequential occurrence of these two diseases, the patients were categorized into three groups: The prePD-MG (30 cases), preMG-PD (12 cases), and coPD-MG (5 cases) groups. In the prePD-MG group, the onset age of MG was older and head drop was more common. In the preMG-PD group, the patients were more likely to have comorbid immune diseases.

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Microglia-mediated neuroinflammation has been largely considered one of main factors to the PD pathology. MicroRNA-218-5p (miR-218-5p) is a microRNA that plays a role in neurodevelopment and function, while its potential function in PD and neuroinflammation remains unclear. Methods We explore the involvement of miR-218-5p in the PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. The miR-218-5p agomir used for overexpression was delivered into the substantia nigra (SN) by bilateral stereotaxic infusions. The loss of dopaminergic (DA) neurons and microglial inflammation in the SN was determined using Western blotting and immunofluorescence. Motor function was assessed using the rotarod test. RNA sequencing (RNA-seq) was performed to explore the pathways regulated by miR-218-5p. The target genes of miR-218-5p were predicted using TargetScan and confirmed using dual luciferase reporter assays. The effects of miR-218-5p on microglial inflammation and related pathways were verified in murine microglia-like BV2 cells. To stimulate BV2 cells, SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP + ) and the conditioned media (CM) were collected. Results MiR-218-5p expression was reduced in both the SN of MPTP-induced mice and MPP + -treated BV2 cells. MiR-218-5p overexpression significantly alleviated MPTP-induced microglial inflammation, loss of DA neurons, and motor dysfunction. RNA sequence and gene set enrichment analysis showed that type I interferon (IFN-I) pathways were upregulated in MPTP-induced mice, while this upregulation was reversed by miR-218-5p overexpression. A luciferase reporter assay verified that Ddx41 was a target gene of miR-218-5p. In vitro, miR-218-5p overexpression or Ddx41 knockdown inhibited the IFN-I response and expression of inflammatory cytokines in BV2 cells stimulated with MPP + -CM. Conclusions MiR-218-5p suppresses microglia-mediated neuroinflammation and preserves DA neurons via Ddx41 /IFN-I. Hence, miR-218-5p- Ddx41 is a promising therapeutic target for PD.

BackgroundParkinson’s disease (PD), which is associated to autoimmune disorders, is characterized by the pathological deposition of alpha-synuclein (α-Syn) and loss of dopaminergic (DA) neurons. Th17 cells are thought to be responsible for the direct loss of DA neurons. C-C chemokine ligand 5 (CCL5) specifically induces Th17 cell infiltration into the SN. However, the specific effect of CCL5 on Th17 cells in PD and the relationship between CCL5 and lymphocyte function-associated antigen-1 (LFA-1) expression in Th17 cells are unknown.MethodsWe evaluated the effects of CCL5 on LFA-1 expression in Th17 cells in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined Th17 cell differentiation upon CCL5 stimulation in vitro. Furthermore, we assessed the effects of CCL5 on tyrosine kinase zeta-chain-associated protein kinase 70 (ZAP70) and lymphocyte-specific protein tyrosine kinase (LCK) activity in CCL5-stimulated Th17 cells in vivo and in vitro.ResultsCCL5 increased the proportion of peripheral Th17 cells in MPTP-treated mice, LFA-1 expression on Th17 cells, and Th17 cell levels in the SN of MPTP-treated mice. CCL5 promoted Th17 cell differentiation and LFA-1 expression in naive T cells in vitro. Moreover, CCL5 increased Th17 cell differentiation and LFA-1 expression by stimulating LCK and ZAP70 activation in naive CD4+ T cells. Inhibiting LCK and ZAP70 activation reduced the proportion of peripheral Th17 cells and LFA-1 surface expression in MPTP-treated mice, and Th17 cell levels in the SN also significantly decreased.ConclusionCCL5, which increased Th17 cell differentiation and LFA-1 protein expression by activating LCK and ZAP70, could increase the Th17 cell number in the SN, induce DA neuron death and aggravate PD.

目的:比较震颤为主型和少动-强直为主型帕金森病(PD)患者心脏自主神经调节功能的差异.方法:收集120例PD患者(震颤为主型、少动-强直为主型各60例),招募同期健康者60例为对照组,分别进行24 h动态心电图检查,收集其一般资料及自主神经功能量表(SCOPA-AUT)评分等,比较各组的SCOPA-AUT评分及心率变异性(HRV)参数.结果:无论震颤为主型还是少动-强直为主型PD患者,其SCOPA-AUT评分高于对照组(P均＜0.001),低频成分(LF)、相邻NN间期差异≥50 ms占所有NN间期总数的百分比(pNN50)均低于对照组(LF:P=0.005,P=0.003;pNN50:P=0.049,P=0.002),而少动-强直为主型PD患者的高频成分(HF)显著低于震颤为主型及对照组(P=0.019,P=0.001),LF/HF与震颤为主型存在差异,24h内全部相邻窦性R-R间期差值的均方根值(rMSSD)、24 h内全部窦性R-R间期的标准差(SDNN)明显低于对照组(P=0.003,P=0.035).结论:帕金森病患者的自主神经功能普遍受损,少动-强直为主型PD患者的自主神经功能受损更严重,迷走神经活性明显降低.

作为一种常见的神经系统疾病，特发性震颤随着基层医疗水平的提高和广大群众生命健康意识的提升，得到了更多的重视和关注。本刊刊出的《特发性震颤基层诊疗指南（2021年）》及实践版，从疾病的定义、分型、诊断、鉴别诊断、治疗、疾病管理等方面给出了具体、实用的指导意见 ［1］，有助于社区医务人员及早识别、诊断和给出合理化的转诊以及治疗建议。作为对指南中手术治疗方面的补充，本文将围绕特发性震颤手术治疗的主题展开，进一步拓展基层医生的诊疗思路，从而为患者提供个体化的治疗建议和预后预测。

BackgroundsThe relationship between kidney function and cognitive impairment in Parkinson’s disease (PD) is poorly understood and underexplored. This study aims to explore whether renal indices can serve as indicators to monitor the cognitive impairment of PD.MethodsA total of 508 PD patients and 168 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI) were recruited, and 486 (95.7%) PD patients underwent longitudinal measurements. The renal indicators including serum creatinine (Scr), uric acid (UA), and urea nitrogen, as well as UA/Scr ratio and estimated glomerular filtration rate (eGFR), were measured. Cross-sectional and longitudinal associations between kidney function and cognitive impairment were evaluated using multivariable-adjusted models.ResultseGFR was associated with lower levels of cerebrospinal fluid (CSF) Aβ1–42 (p = 0.0156) and α-synuclein (p = 0.0151) and higher serum NfL (p = 0.0215) in PD patients at baseline. Longitudinal results showed that decreased eGFR predicted a higher risk of cognitive impairment (HR = 0.7382, 95% CI = 0.6329–0.8610). Additionally, eGFR decline was significantly associated with higher rates of increase in CSF T-tau (p = 0.0096), P-tau (p = 0.0250), and serum NfL (p = 0.0189), as well as global cognition and various cognitive domains (p < 0.0500). The reduced UA/Scr ratio was also linked to higher NfL levels (p = 0.0282) and greater accumulation of T-tau (p = 0.0282) and P-tau (p = 0.0317). However, no significant associations were found between other renal indices and cognition.ConclusioneGFR is altered in PD subjects with cognitive impairment, and predict larger progression of cognitive decline. It may assist identifying patients with PD at risk of rapid cognitive decline and have the potential to monitoring responses to therapy in future clinical practice.

BACKGROUND One-fourth of Parkinson's disease (PD) patients suffer from cognitive impairment. However, few neuroimaging markers have been identified regarding cognitive impairment in PD. OBJECTIVE This study aimed to explore the association between third ventricular width by transcranial sonography (TCS) and cognitive decline in PD. METHOD Participants with PD were recruited from one medical center in China. Third ventricular width was assessed by TCS, and cognitive function was analyzed by the Mini-Mental State Examination (MMSE). Receiver operating characteristic (ROC) analysis and Cox model analysis were utilized to determine the diagnostic and predictive accuracy of third ventricular width by TCS for cognitive decline in PD patients. RESULT A total of 174 PD patients were recruited. Third ventricular width was negatively correlated with MMSE scores. ROC analysis suggested that the optimal cutoff point for third ventricular width in screening for cognitive impairment in PD was 4.75 mm (sensitivity 62.7%; specificity 75.6%). After 21.5 (18.0, 26.0) months of follow-up in PD patients without cognitive impairment, it was found that those with a third ventricular width greater than 4.75 mm exhibited a 7.975 times higher risk of developing cognitive impairment [hazard ratio = 7.975, 95% CI 1.609, 39.532, p = 0.011] compared with patients with a third ventricular width less than 4.75 mm. CONCLUSION Third ventricular width based on TCS emerged as an independent predictor of developing cognitive impairment in PD patients.

BACKGROUND:Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons (DA) and the accumulation of Lewy body deposits composed of alpha-Synuclein (α-Syn), which act as antigenic epitopes to drive cytotoxic T-cell responses in PD. Increased T helper 17 (Th17) cells and dysfunctional regulatory T cells (Tregs) have been reported to be associated with the loss of DA in PD. However, the mechanism underlying the Th17/Treg imbalance remains unknown.METHODS:Here, we examined the percentage of Th17 cells, the percentage of Tregs and the α-Syn level and analysed their correlations in the peripheral blood of PD patients and in the substantia nigra pars compacta (SNpc) and spleen of MPTP-treated mice and A53 transgenic mice. We assessed the effect of α-Syn on the stability and function of Tregs and the differentiation of Th17 cells and evaluated the role of retinoid-related orphan nuclear receptor (RORγt) upregulation in α-Syn stimulation in vivo and in vitro.RESULTS:We found that the α-Syn level and severity of motor symptoms were positively correlated with the increase in Th17 cells and decrease in Tregs in PD patients. Moreover, α-Syn stimulation led to the loss of Forkhead box protein P3 (FOXP3) expression in Tregs, accompanied by the acquisition of IL-17A expression. Increased Th17 differentiation was detected upon α-Syn stimulation when naïve CD4+ T cells were cultured under Th17-polarizing conditions. Mechanistically, α-Syn promotes the transcription of RORC, encoding RORγt, in Tregs and Th17 cells, leading to increased Th17 differentiation and loss of Treg function. Intriguingly, the increase in Th17 cells, decrease in Tregs and apoptosis of DA were suppressed by a RORγt inhibitor (GSK805) in MPTP-treated mice.CONCLUSION:Together, our data suggest that α-Syn promotes the transcription of RORC in circulating CD4+ T cells, including Tregs and Th17 cells, to impair the stability of Tregs and promote the differentiation of Th17 cells in PD. Inhibition of RORγt attenuated the apoptosis of DA and alleviated the increase in Th17 cells and decrease in Tregs in PD.