Mechanisms of oxidative damage in MS and neurodegenerative diseases: therapeutic modulation via fumaric acid esters


This study reviews the role of oxidative stress in neurodegenerative conditions, in particular MS. Recent data has highlighted the important role of anti-oxidative pathways for tissue protection in chronic-progressive MS, especially transcription factor nuclear factor (erythroid-derived 2) related factor 2 (Nrf2).

Based on this, novel therapies, like fumaric acid esters (FAE), which is a new oral available treatment which has been tested in phase II/III trials, demonstrate positive outcomes on both relapse rate and MRI markers. At the cellular level, the application of fumaric acid esters enhances neuronal survival and protects astrocytes against oxidative stress. The use of fumaric acid esters involves direct modification of the inhibitor of Nrf2, Kelch-like ECH-associated protein 1. Oxidative stress plays an important role in the pathophysiology of MS and is a very promising target for future therapies like fumeric acid esters.

Authors: Lee DH, Gold R, Linker RA

Source:
Int J Mol Sci. 2012;13(9):11783-803. Epub 2012 Sep 18.

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