Inhibition of noradrenaline synthesis by clioquinol, the causative agent of subacute myelo-optic neuropathy (SMON)

Abstract

Clioquinol is regarded as the causative agent of subacute myelo-optic neuropathy (SMON). Yet, the pathogenesis of SMON has not been fully elucidated. In human neuroblastoma SH-SY5Y cells, clioquinol induced the oxidation of ATOX1, suggesting its inactivation and inhibition of copper transport. The secretion of dopamine-β-hydroxylase, a copper-dependent enzyme, was inhibited by clioquinol, along with decreased noradrenaline levels. The disturbance of cellular copper transport by the inactivation of ATOX1 may be one of the mechanisms involved in clioquinol-induced neurotoxicity in SMON.