Parkinson's disease (PD) is a common neurodegenerative disorder that featured by the loss of dopaminergic neurons. Astaxanthin (AST), an important antioxidant, is demonstrated to be a neuroprotective agent for PD. However, the underlying mechanisms of AST in PD remain largely unclear. In this study, we found that AST treatment significantly not only abolished the cell viability inhibition and apoptosis promotion induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells via inhibiting endoplasmic reticulum (ER) stress, but also reversed the MPP + caused dysregulation of miR-7 and SNCA expression. MiR-7 knockdown and SNCA overexpression were achieved by treating SH-SY5Y cells with miR-7 inhibitor and pcDNA3.1-SNCA plasmids, respectively. MiR-7 could bind to and negatively regulate SNCA in SH-SY5Y cells. Treated SH-SY5Y cells with miR-7 inhibitor or pcDNA3.1-SNCA abrogated the protective effects of AST on MPP + induced cytotoxicity. Knockdown of miR-7 aggravated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neuron injury in vivo suggested by athletic performance, histopathological morphology, expression of tyrosine hydroxylase (TH) and TUNEL positvie cells, however, AST treatment could reverse these effects of miR-7 knockdown. Collectively, AST suppressed ER stress and protected against PD-caused neuron damage by targeting miR-7/SNCA axis, implying that AST might be a potential effective therapeutic agent for PD.

中文翻译：

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虾青素通过调节 miR-7/SNCA 轴抑制内质网应激并防止帕金森病神经元损伤

帕金森病 (PD) 是一种常见的神经退行性疾病，其特征是多巴胺能神经元的丧失。虾青素 (AST) 是一种重要的抗氧化剂，已被证明是 PD 的神经保护剂。然而，AST 在 PD 中的潜在机制在很大程度上仍不清楚。在本研究中，我们发现AST处理不仅通过抑制内质网（ER）应激，显着消除了SH-SY5Y细胞中1-甲基-4-苯基吡啶（MPP+）诱导的细胞活力抑制和凋亡促进作用，而且逆转了MPP + 引起 miR-7 和 SNCA 表达的失调。通过分别用 miR-7 抑制剂和 pcDNA3.1-SNCA 质粒处理 SH-SY5Y 细胞来实现 MiR-7 敲低和 SNCA 过表达。MiR-7 可以结合并负调节 SH-SY5Y 细胞中的 SNCA。用 miR-7 抑制剂或 pcDNA3.1-SNCA 处理的 SH-SY5Y 细胞消除了 AST 对 MPP + 诱导的细胞毒性的保护作用。运动表现、组织病理学形态、酪氨酸羟化酶 (TH) 和 TUNEL 阳性细胞的表达表明 miR-7 的敲低加剧了 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的体内神经元损伤然而，AST 处理可以逆转 miR-7 敲低的这些影响。总的来说，AST 通过靶向 miR-7/SNCA 轴来抑制 ER 应激并防止 PD 引起的神经元损伤，这意味着 AST 可能是 PD 的潜在有效治疗剂。运动表现、组织病理学形态、酪氨酸羟化酶 (TH) 和 TUNEL 阳性细胞的表达表明 6-四氢吡啶 (MPTP) 在体内诱导神经元损伤，然而，AST 治疗可以逆转 miR-7 敲低的这些影响。总的来说，AST 通过靶向 miR-7/SNCA 轴来抑制 ER 应激并防止 PD 引起的神经元损伤，这意味着 AST 可能是 PD 的潜在有效治疗剂。运动表现、组织病理学形态、酪氨酸羟化酶 (TH) 和 TUNEL 阳性细胞的表达表明 6-四氢吡啶 (MPTP) 在体内诱导神经元损伤，然而，AST 治疗可以逆转 miR-7 敲低的这些影响。总的来说，AST 通过靶向 miR-7/SNCA 轴来抑制 ER 应激并防止 PD 引起的神经元损伤，这意味着 AST 可能是 PD 的潜在有效治疗剂。