Montalbán-Rodríguez Alba, Abalo Raquel, López-Gómez Laura
Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcon, Spain.
High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain.
Int J Mol Sci. 2024 Jan 20;25(2):1294. doi: 10.3390/ijms25021294.
The brain-gut axis has been identified as an important contributor to the physiopathology of Parkinson's disease. In this pathology, inflammation is thought to be driven by the damage caused by aggregation of α-synuclein in the brain. Interestingly, the Braak's theory proposes that α-synuclein misfolding may originate in the gut and spread in a "prion-like" manner through the vagus nerve into the central nervous system. In the enteric nervous system, enteric glial cells are the most abundant cellular component. Several studies have evaluated their role in Parkinson's disease. Using samples obtained from patients, cell cultures, or animal models, the studies with specific antibodies to label enteric glial cells (GFAP, Sox-10, and S100β) seem to indicate that activation and reactive gliosis are associated to the neurodegeneration produced by Parkinson's disease in the enteric nervous system. Of interest, Toll-like receptors, which are expressed on enteric glial cells, participate in the triggering of immune/inflammatory responses, in the maintenance of intestinal barrier integrity and in the configuration of gut microbiota; thus, these receptors might contribute to Parkinson's disease. External factors like stress also seem to be relevant in its pathogenesis. Some authors have studied ways to reverse changes in EGCs with interventions such as administration of Tryptophan-2,3-dioxygenase inhibitors, nutraceuticals, or physical exercise. Some researchers point out that beyond being activated during the disease, enteric glial cells may contribute to the development of synucleinopathies. Thus, it is still necessary to further study these cells and their role in Parkinson's disease.
脑-肠轴已被确认为帕金森病病理生理学的一个重要促成因素。在这种病理状态下，炎症被认为是由大脑中α-突触核蛋白聚集所造成的损伤驱动的。有趣的是，布拉克理论提出α-突触核蛋白错误折叠可能起源于肠道，并以“朊病毒样”方式通过迷走神经扩散至中枢神经系统。在肠神经系统中，肠胶质细胞是最丰富的细胞成分。多项研究评估了它们在帕金森病中的作用。利用从患者、细胞培养物或动物模型中获取的样本，使用特异性抗体标记肠胶质细胞（胶质纤维酸性蛋白、Sox-10和S100β）的研究似乎表明，激活和反应性胶质增生与帕金森病在肠神经系统中产生的神经退行性变有关。有趣的是，表达于肠胶质细胞上的Toll样受体参与免疫/炎症反应的触发、肠道屏障完整性的维持以及肠道微生物群的构成；因此，这些受体可能与帕金森病有关。压力等外部因素在其发病机制中似乎也很重要。一些作者研究了通过诸如给予色氨酸-2,3-双加氧酶抑制剂、营养保健品或体育锻炼等干预措施来逆转肠胶质细胞变化的方法。一些研究人员指出，除了在疾病期间被激活外，肠胶质细胞可能有助于突触核蛋白病的发展。因此，仍有必要进一步研究这些细胞及其在帕金森病中的作用。
