Singh Amrendra Pratap, Ramana G, Bajaj Teena, Singh Vishwajeet, Dwivedi Sadanand, Behari Madhuri, Dey A B, Dey Sharmistha
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Front Mol Neurosci. 2019 Jun 12;12:129. doi: 10.3389/fnmol.2019.00129. eCollection 2019.
Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson's disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric α-synuclein (α-Syn), a key element in the pathogenesis of PD, with Sirtuin (SIRT)2 proteins for modulating PD. We aimed to evaluate SIRT protein expression in serum of PD patients and compare it with APSs and normal elderly control (GC) and to correlate this with α-Syn. SIRT protein expression was evaluated in sera of 68 PD; 34 APS and 68 GC without any neuro-psychiatric illness as controls by surface plasmon resonance (SPR). SIRT2 expression was correlated with α-Syn in PD and GC. Significant ( < 0.0001) differences were observed between serum SIRT2 concentration in PD and APS and GC as well as between APS and GC. Receiver operating characteristic (ROC) analysis revealed the strong cut-off value to differentiate PD from APS and GC and also APS from GC. Significant correlation was observed among SIRT2 levels in early PD patients with Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H & Y) and increased duration of disease. In addition, a strong positive correlation of SIRT2 with α-Syn ( < 0.0001) was observed. However, no such difference was detected for serum SIRT1 in cases of PD and APS or for GC. The present study is the first to report elevated serum SIRT2 in PD. The study also provided a simple test to distinguish PD from APS and may have translational utility for diagnosis.
非典型帕金森综合征（APSs）的症状常与帕金森病（PD）重叠，尤其是在疾病早期，这使得这些疾病难以诊断。先前的研究已证明，寡聚α-突触核蛋白（α-Syn）是PD发病机制中的关键要素，与沉默调节蛋白（SIRT）2蛋白在调节PD方面存在关联。我们旨在评估PD患者血清中的SIRT蛋白表达，并将其与APSs患者及正常老年对照（GC）进行比较，同时将其与α-Syn进行关联分析。通过表面等离子体共振（SPR）技术，对68例PD患者、34例APS患者以及68例无任何神经精神疾病的GC患者血清中的SIRT蛋白表达进行了评估。在PD患者和GC患者中，对SIRT2表达与α-Syn进行了相关性分析。结果发现，PD患者与APS患者及GC患者血清中SIRT2浓度之间存在显著差异（<0.0001），APS患者与GC患者之间也存在显著差异。受试者工作特征（ROC）分析显示，有较强的临界值可用于区分PD与APS及GC，以及区分APS与GC。早期PD患者的SIRT2水平与统一帕金森病评定量表（UPDRS）、霍恩和亚尔分级（H&Y）以及病程延长之间存在显著相关性。此外，还观察到SIRT2与α-Syn之间存在强正相关（<0.0001）。然而，在PD和APS患者或GC患者中，未检测到血清SIRT1有此类差异。本研究首次报道了PD患者血清中SIRT2升高。该研究还提供了一种简单的检测方法来区分PD与APS，可能具有诊断方面的转化应用价值。
