a Neurosciences Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
b Department of Biochemistry and Clinical Laboratories, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.
Nutr Neurosci. 2018 Feb;21(2):92-96. doi: 10.1080/1028415X.2016.1239399. Epub 2016 Oct 4.
Multiple sclerosis (MS) is a disease which manifests demyelination of neuronal cells in the brain. Despite extensive research on the mechanisms of disease development and progression, the exact mechanism is not elucidated yet, which has hampered drug development and subsequent treatment of the disease. We have recently shown that the serum levels of arsenic and malondialdehyde, a lipid peroxidation marker, are high in MS patients. In this article, we would like to formulate the hypothesis that arsenic may cause MS by induction of inflammation, degeneration, and apoptosis in neuronal cells. The induction of ROS generation in cells upon exposure to arsenic as a heavy metal may be involved in the pathogenesis of MS. Tau protein, a member of the family of microtubule-associated proteins, is mainly expressed in neurons and contribute to the assembly of neuronal microtubules network. Arsenic may affect the hyperphosphorylation and aggregation of tau proteins and may be involved in the cascade leading to deregulation of tau function associated with neurodegeneration. For validation of this hypothesis, studies might be conducted to evaluate the association of arsenic levels and tau protein levels in MS patients. Further studies might also focus on the trafficking along microtubules in neurons of MS patient with regard to hyperphosphorylation of tau protein. This hypothesis may add a new dimension to the understanding of MS etiology and help to design novel therapeutic agents against potential targets that might be discovered. If this hypothesis proves to be true, tau phosphorylation inhibitors can be potential candidates for MS drug development.
多发性硬化症（MS）是一种表现为大脑神经元细胞脱髓鞘的疾病。尽管对疾病发展和进展的机制进行了广泛的研究，但确切的机制尚未阐明，这阻碍了药物的开发和随后对疾病的治疗。我们最近表明，MS 患者的血清砷和丙二醛（脂质过氧化标志物）水平较高。在本文中，我们提出假设，认为砷可能通过诱导神经元细胞的炎症、变性和细胞凋亡而导致 MS。砷作为重金属暴露于细胞时诱导 ROS 生成，可能参与 MS 的发病机制。微管相关蛋白家族的成员 tau 蛋白主要在神经元中表达，并有助于神经元微管网络的组装。砷可能会影响 tau 蛋白的过度磷酸化和聚集，并可能参与导致与神经退行性变相关的 tau 功能失调的级联反应。为了验证这一假设，可以进行研究来评估 MS 患者中砷水平和 tau 蛋白水平之间的关联。进一步的研究也可能集中在 MS 患者神经元中微管上的 tau 蛋白过度磷酸化的运输上。这一假设可能为理解 MS 的病因学增加一个新的维度，并有助于设计针对可能发现的潜在靶点的新型治疗药物。如果这一假设被证明是正确的，tau 磷酸化抑制剂可能是 MS 药物开发的潜在候选药物。
