Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis.

Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis. Eur J Pharmacol. 2020 Feb 01;:172973 Authors: Michaličková D, Hrnčíř T, Canová NK, Slanař O Abstract Multiple sclerosis (MS) is a neurologic autoimmune disorder featured by chronic inflammation of the central nervous system, demyelination and axonal damage. Recently, the term "oxinflammation" has been proposed to depict the vicious circle of chronic inflammation and oxidative stress (OS). OS promotes demyelination and neurodegeneration directly, by oxidation of lipids, proteins, and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. Many of the actors of this delicately tuned network are controlled by Keap1/Nrf2/ARE signaling pathway, a principal regulator of antioxidant and phase II detoxification genes. This pathway also has a pivotal role in inflammation, and therefore possesses a great potential in the treatment of MS. The aim of this review is to provide the newest insights in the preclinical and clinical evidence of Nrf2 induction in the regeneration of the antioxidant response and attenuation of inflammation in MS. Preclinical studies have indicated that activators of this pathway, such as epigallocatechin gallate (EGCG), curcumin, melatonin, resveratrol, and sulforaphane might be a promising therapeutic option in amelioration of MS symptoms, nevertheless, the efficacy and safety of th...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research