Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Neurosci Lett. 2019 Jun 21;704:45-49. doi: 10.1016/j.neulet.2019.03.054. Epub 2019 Apr 1.
Alpha-synuclein (α-SYN) is found in peripheral autonomic neuronal network apart from brain in Parkinson's disease (PD). Nitrated α-SYN is an undesirable modification associated with oxidative and nitrative damage and has been found extensively in brain, gastrointestinal(GI) tract and blood cells in PD. We aim to investigate the presence of nitrated α-SYN in minor salivary gland biopsy in PD. Patients with PD and age-matched controls underwent minor salivary gland biopsy. Motor impairment was assessed by Hoehn-Yahr (H-Y) stage and Unified Parkinson's Disease Rating Scale (UPDRS) Part III in off-state. 11C-methyl-N-2b-carbomethoxy-3b-(4-fluorophenyl) tropane (11C-CFT) DAT-PET scan was performed in all subjects. Immunohistochemical staining for nitrated α-SYN was performed in the minor salivary gland tissues. The minor salivary gland tissues of 8 PD cases and 7 controls with early stage (H-Y stage 1-2) were detected. All PD patients showed asymmetrical and reduction of C-CFT uptake in the caudate, anterior and posterior putamen, while all control subjects showed normal DAT-PET scan. Positive nitrated α-SYN immunostaining was observed in all PD patients (8/8,100%) but not in control subjects (0/7). The results were consistent well with that of DAT-PET. These nitrated alpha-synuclein positive structures were mainly located in the periacinar stroma in PD patients. Our result suggests that nitrated α-SYN exists in the early stage and is probably a promising biomarker for PD. Minor salivary gland is an ideal site for α-SYN nitration detection. Despite of the small number of subjects, attention should be given to α-SYN nitration in PD and more investigations on nitrated α-SYN in different sites and large sample using should be explored in future.
α-突触核蛋白（α-SYN）除了在大脑中，在帕金森病（PD）患者的周围自主神经网络中也有发现。硝化的α-SYN 是一种与氧化和硝化损伤相关的不理想修饰物，已在 PD 患者的大脑、胃肠道（GI）道和血细胞中广泛发现。我们旨在研究 PD 患者的小唾液腺活检中是否存在硝化的α-SYN。PD 患者和年龄匹配的对照组接受了小唾液腺活检。在非活动状态下，使用 Hoehn-Yahr（H-Y）分期和统一帕金森病评定量表（UPDRS）第三部分评估运动障碍。所有受试者均进行 11C-甲基-N-2b-羧甲基-3b-（4-氟苯基）托烷（11C-CFT）DAT-PET 扫描。在小唾液腺组织中进行硝化的α-SYN 免疫组织化学染色。检测了 8 例 PD 病例和 7 例早期（H-Y 分期 1-2）对照组的小唾液腺组织。所有 PD 患者均表现出尾状核、前、后壳核的 C-CFT 摄取不对称减少，而所有对照组的 DAT-PET 扫描均正常。8 例 PD 患者（100%）均有硝化α-SYN 免疫染色阳性，而对照组（0/7）均无。结果与 DAT-PET 一致。这些硝化的α-突触核蛋白阳性结构主要位于 PD 患者的腺周基质中。我们的结果表明，硝化的α-SYN 存在于早期，可能是 PD 的一个有前途的生物标志物。小唾液腺是检测α-SYN 硝化的理想部位。尽管研究对象数量较少，但应注意 PD 中的α-SYN 硝化，并在未来探索使用不同部位和大样本对硝化的α-SYN 进行更多研究。
