Horizons in Neuroscience Research

Neurotoxic and Inflammatory Mediators Elicited by Astrocytes and Microglia in Response to Myelin Basic Protein (MBP)


Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease that occurs within the central nervous system (CNS). This debilitating disease leads to severe impairments in motor function as well as altered gait, balance difficulty, visual disturbances, and cognitive dysfunction. These symptoms are the result of inflammation, demyelination, and neuronal damage and death. There is evidence which suggests that resident CNS cells may be involved in perpetuating the neuronal injury that occurs during the disease state. As demyelination occurs within the CNS, astrocytes and microglia are able to interact with myelin breakdown products, specifically myelin basic protein (MBP). The binding of MBP by astrocytes and microglia leads to their activation. This results in the secretion of neurotoxic and inflammatory mediators. These mediators elicit further damage to the neurons, thereby propagating neuronal injury and death. This chapter will illustrate how astrocytes and microglia respond to MBP and in turn elicit neurotoxic and inflammatory mediators. The mediators discussed will include CCL-2, tumor necrosis factor-alpha, glutamate, and nitric oxide. The role of these mediators in neurodegeneration will be examined, and possible mechanisms for therapy will also be considered.

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