Capacity of fullerenols to modulate neurodegeneration induced by ferroptosis: Focus on multiple sclerosis

Abstract

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS), characterized by oligodendrocyte loss and demyelination of axons leading to neurodegeneration and severe neurological disability. Despite the existing drugs that have immunomodulatory effects an adequate therapy that slow down or stop neuronal death has not yet been found. Oxidative stress accompanied by excessive release of iron into the extracellular space, mitochondrial damage and lipid peroxidation are important factors in the controlled cell death named ferroptosis, latterly recognized in MS. As the fullerenols exhibit potent antioxidant activity, recent results imply that they could have protective effects by suppressing ferroptosis. Based on the current knowledge we addressed the main mechanisms of the protective effects of fullerenols in the CNS in relation to ferroptosis. Inhibition of inflammation, iron overload and lipid peroxidation through the signal transduction mechanism of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2), chelation of heavy metals and free radical scavenging using fullerenols are proposed as benefitial strategy preventing MS progression. Current review connects ferroptosis molecular targets and important factors of MS progression, with biomedical properties and mechanisms of fullerenols' actions, to propose new treatment strategies that could be addaptobale in other neurodegenerative diseases.

Keywords: Ferroptosis; Fullerenol; Mitochondrial dysfunction; Multiple sclerosis; Neurodegeneration; Oxidative stress.