The hypothetical roles of arsenic in multiple sclerosis by induction of inflammation and aggregation of tau protein: A commentary

Abstract

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.

Toxic heavy metal concentrations in multiple sclerosis patients: a systematic review and meta-analysis

“…One of the most toxic naturally occurring metals, As is a peripheral neurotoxicant capable of inducing nervous system damages and neuropathy (Yousefi et al, 2014[ 48 ]; Alizadeh-Ghodsi et al, 2018[ 4 ]). This toxicant can induce or intensify many diseases including MS by producing oxidative stress (Jomova et al, 2011[ 21 ]).…”

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis

“…The new use of old drugs is an effective way of developing new drugs. Although evidence showing that arsenic may be associated with the risk of developing MS or MS progression [57][58][59][60], the types of arsenic compounds involved in MS pathogenesis remain unclear. Our results suggested that ATO could effectively ameliorate symptoms of EAE in MOG-induced EAE mice.…”

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

“…The discrepancy in between pro-oxidant and antioxidant ratio leads to the generation of ROS significant oxidative stress. Arsenic exposure increases TBARS level (LPO) in the hippocampus ( Ashok et al., 2015 ; Kumar et al., 2013 ), which may culminate into neuronal damage as it causes oxidative degradation of the cellular macromolecules leading to neurodegeneration ( Alizadeh-Ghodsi et al., 2016 ; Cholanians et al., 2016 ; Escudero-Lourdes, 2016 ). A significant increase in the level of LPO was observed that correlates with weak antioxidant defense mechanism or inactivation of antioxidant enzymes such as SOD ( Muthumani and Miltonprabu, 2015 ; Prakash and Kumar, 2016 ; Prakash et al., 2015 ).…”