Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP, 226014, India.
Metab Brain Dis. 2022 Jan;37(1):209-217. doi: 10.1007/s11011-021-00801-9. Epub 2021 Aug 3.
Parkinson's disease (PD) and Parkinsonian syndromes; Progressive supranuclear palsy (PSP), and Multiple system atrophy (MSA) are debilitating neurodegenerative disorders. Fractalkine is a chemokine involved in neuroinflammation, whereas, 3-nitrotyrosine (3-NT) is a marker of early neurodegenerative cellular-damage. We measured Fractalkine and 3-NT levels in the serum of these patients to examine the neuroinflammation hypothesis and also to decipher the propensity of these biologics to be used as early (5 years from onset) biochemical markers in neurodegenerative Parkinsonism. The diagnoses of PD, PSP and MSA were performed as per the respective clinical criteria. 21 PD, 9 PSP and 8 MSA patients along with controls participated in this study. Serum concentrations of Fractalkine and 3-NT were measured by ELISA. Fractalkine levels were increased in PD, PSP and MSA cohorts in comparison with controls with p < 0.001, p < 0.05 and p < 0.05 respectively. Levels of 3-NT also showed elevation in PD (p < 0.01) vs. controls. However, Pearson plot showed that Fractalkine levels were high in the patients with unified Parkinson's disease rating scale (UPDRS) part III motor score of 1, meaning slight disability, but gradually dropped in patients with motor score of 4, which is a measure of severe motor disability. This negative correlation (- .565, p < .0.01) also accentuates the neuroprotectant/anti-inflammatory nature of Fractalkine in PD. Continuous rise of 3-NT in PD, positively correlating (.512, p < 0.05) with worsening motor symptoms points to deleterious consequences of nitrosative stress. To our knowledge, this is the first report providing evidence that serum Fractalkine and 3-NT have early diagnostic/prognostic significance as PD biomarkers.
帕金森病(PD)和帕金森综合征;进行性核上性麻痹(PSP)和多系统萎缩(MSA)是使人衰弱的神经退行性疾病。趋化因子 fractalkine 参与神经炎症,而 3-硝基酪氨酸(3-NT)是早期神经退行性细胞损伤的标志物。我们测量了这些患者血清中的 fractalkine 和 3-NT 水平,以检验神经炎症假说,并阐明这些生物标志物是否有潜力作为神经退行性帕金森病的早期(发病后 5 年)生化标志物。PD、PSP 和 MSA 的诊断是根据各自的临床标准进行的。21 名 PD、9 名 PSP 和 8 名 MSA 患者以及对照组参与了这项研究。通过 ELISA 测量血清 fractalkine 和 3-NT 浓度。与对照组相比,PD、PSP 和 MSA 组的 fractalkine 水平均升高,p<0.001、p<0.05 和 p<0.05。PD 组的 3-NT 水平也升高(p<0.01)。然而,Pearson 图显示,在统一帕金森病评定量表(UPDRS)第三部分运动评分 1 的患者中,fractalkine 水平较高,这意味着轻微残疾,但在运动评分 4 的患者中,fractalkine 水平逐渐下降,这是严重运动残疾的衡量标准。这种负相关(-0.565,p<0.01)也强调了 fractalkine 在 PD 中的神经保护/抗炎特性。PD 中 3-NT 的持续升高,与运动症状的恶化呈正相关(0.512,p<0.05),表明硝化应激的有害后果。据我们所知,这是首次提供证据表明,血清 fractalkine 和 3-NT 具有作为 PD 生物标志物的早期诊断/预后意义。