title: 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.
authors.affiliation: 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.
authors.forename: Mohammadreza
authors.identifier: http://orcid.org/0000-0001-9454-3222
authors.initials: M
authors.lastname: Alizadeh-Ghodsi
authors.affiliation: b Department of Biochemistry and Clinical Laboratories, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.|c Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Zavvari
authors.affiliation: a Neurosciences Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|d Neurosciences Department, School of Advanced Medical Sciences , Tabriz University of Medical Sciences, Tabriz , Iran.
authors.forename: Abbas
authors.identifier: http://orcid.org/0000-0001-5466-6754
authors.initials: A
authors.lastname: Ebrahimi-Kalan
authors.affiliation: e Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, International Campus , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Shiri-Shahsavar
authors.affiliation: c Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|f Students' Research Committee , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Yousefi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001151:Arsenic / Q000633:toxicity*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000175:diagnosis*; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000097:blood; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000175:diagnosis*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological / Q000139:chemically induced / Q000175:diagnosis*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D008315:Malondialdehyde; D001151:Arsenic
keywords: Arsenic; Multiple sclerosis; Neurodegeneration; Oxidative stress; Tau protein