Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?

National Centre for Multiple Sclerosis, B 1820 Melsbroek, Belgium

^* To whom correspondence should be addressed.

	Abstract

There is increasing evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. In neurodegenerative diseases, neuronal and axonal loss is mediated by oxidative stress and excitotoxicity which constitute a final common toxic pathway. Importantly, peroxynitrite is the key mediator of those two intertwined pathomechanisms. In MS, peroxynitrite is consistently associated with active lesions and produces highly toxic nitrating and oxidizing radical species that alter lipid, protein, DNA and mitochondrial structures and functions. During the remitting phase, peroxynitrite participates to neuron and oligodendrocyte damage in association with inflammatory processes. During the chronic phase, peroxynitrite contributes to self-perpetuating mechanisms responsible for disease progression. Neutralization of oxidative stress and excitotoxicity, and in particular of peroxynitrite derived free radicals, might represent a therapeutic approach to provide neuroprotection in MS.

Key Words: endogenous neuroprotection; excitotoxicity; inosine; multiple sclerosis; oxidative stress; uric acid

First published on September 19, 2007, doi:10.1177/1352458507080111

Multiple Sclerosis 2008;14:22.

A more recent version of this article appeared on January 1, 2008


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