Neuroprotection and repair by neurotrophic and gliotrophic factors in multiple sclerosis

Based on the efficacy of immunomodulatory therapies in patients with multiple sclerosis (MS), much of the research and thinking about pathogenesis and treatment has traditionally focused on suppressing the immune system. Whatever the cause, recent studies have rekindled the notion that neurologic dysfunction in patients with MS relates best to the degree of neuronal (axonal) and glial damage. Therefore, as a means to understand the pathogenesis of MS and to develop biologically targeted new therapeutics, a greater understanding of axoglial biology is needed. Central to axoglial biology are protein regulatory factors that include gliotrophic factors such as the neuregulins and neurotrophic factors that communicate between these cell types and are critical for nervous system development. Unfortunately, the track record of neurotrophic factors for treating other neurologic disorders has not been impressive, in part because of a failure to aim these factors at appropriate pathophysiologic targets. Although future therapeutic strategies in MS may be able to take advantage of these factors, such strategies will require an in-depth understanding of how these factors signal and how they are naturally targeted to axons and glia in both health and disease.