Response to Mousavizadeh et al.: Oxidative toxicity and glutamate excitotoxicity in multiple sclerosis

摘要

In their letter to TiPS [1] in response to our recent TiPS review [2], Mousavizadeh et al. note a role for antioxidants such as uric acid or its precursor inosine as anti-inflammatory and/or immunomodulatory agents in the treatment of multiple sclerosis (MS). Indeed, the natural peroxynitrite scavenger uric acid and its precursors have been demonstrated to ameliorate the clinical course of experimental allergic encephalomyelitis (EAE) in animal models [3,4].Here, we briefly discuss future treatment options in MS that target: (i) oxidative toxicity; and (ii) glutamate excitotoxicity. As shown in Figure 1 of our review [2], oxidants such as oxygen radicals and reactive nitrogen oxide species [e.g. nitric oxide (NO) or peroxynitrite] are major inflammatory mediators of demyelination. NO is generated by the enzyme inducible nitric oxide synthase (iNOS) both in macrophages following activation by autoaggressive T cells and in astrocytes [5].