Departamento de Neuroquímica, Instituto Nacional de Neurología and Neurocirugía, Tlalpan, Ciudad de Mexico 14269, Mexico.
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de Mexico 04510, Mexico.
Int J Mol Sci. 2023 Jun 21;24(13):10414. doi: 10.3390/ijms241310414.
Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP-induced damage compared to the MPP treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.
帕金森病是一种神经退行性疾病，其特征是黑质纹状体通路上的氧化应激和免疫激活。辛伐他汀调节胆固醇代谢，可预防动脉粥样硬化疾病。在大鼠纹状体内立体定位注射 MPP（1-甲基-4-苯基吡啶）前 7 天给予辛伐他汀-吐温 80。荧光脂质产物形成、多巴胺水平和转圈行为被认为是损伤标志物。MPP 处理组的动物在 24 小时和 6 天后与对照组相比表现出明显的损伤。与 MPP 处理组相比，辛伐他汀预处理的动物显著减轻了 MPP 诱导的损伤。由于细胞凋亡会促进帕金森病中的神经炎症和神经元变性，并且目前尚无大鼠黑质纹状体的蛋白质组图谱，并且假设在其他大鼠组织中鉴定的蛋白质之间存在高度同源性，因此我们基于寻找与炎症反应建立相关的大鼠蛋白同源物的研究。我们证明，与炎症相关的大多数蛋白质在辛伐他汀处理的大鼠中减少。此外，还发现了应激反应中大鼠大脑纹状组织中抗氧化酶的差异表达。这些结果表明，辛伐他汀可以预防纹状体 MPP 诱导的损伤，并且首次表明涉及的分子机制具有保护作用。
