2026 Volume 49 Issue 11 Pages 1794-1801
Subacute myelo-optic neuropathy (SMON) is a neuronal disorder that is characterized by early sharp abdominal pain followed by the subacute onset of sensory and motor disturbances in the lower extremities with occasional visual impairments. It occurred mainly in Japan in the mid-1900s, and localized outbreaks of SMON led to the idea of it being an endemic or infectious disease. SMON became a significant social issue in Japan with the spread of its viral etiology. In 1970, the increased incidence of SMON was epidemiologically related to the use of clioquinol (Quinoform), which was extensively administered to treat indigestion and diarrhea, because green substances often noted in the urine of SMON patients were identified as a ferric chelate of clioquinol. Although many studies have since been performed on the toxicity of clioquinol, the pathogenesis of SMON remains unclear. To obtain more detailed insights into the neurotoxicity of clioquinol, we first performed a global analysis of human neuroblastoma cells using DNA chips. By focusing on genes affected by clioquinol and analyzing their expressional regulation, we identified multiple pathways that were suggested to be involved in cell death, mitochondrial toxicity, pain reaction, and loss of neuronal function induced by clioquinol. This review summarizes the history of SMON and clioquinol, research on the neurotoxicity of clioquinol, including our works, and discussion whether specific gene polymorphisms contribute to sensitivity to the toxicity of clioquinol.
