Abstract

Multiple sclerosis (MS) is characterized by demyelinating lesions disseminated throughout the central nervous system, and a progressive axonal degeneration. In this review we propose that an impaired cAMP signaling in white mater astrocytes, caused by a deficiency of β2-adrenergic receptors, may play a role in the pathogenesis of the disease. Reduced astrocytic cAMP signaling may, in a proinflammatory environment, facilitate astrocytes to become facultative antigen presenting cells, stimulating the development of inflammatory demyelinating lesions. It may reduce astrocytic glycogenolysis, which supplies energy and N-acetylaspartate (NAA) to axons and oligodendrocytes, reduce trophic and neuroprotective support to oligodendrocytes and neurons, and enhance astrogliosis.

Keywords: Multiple sclerosis, astrocytes, β2-adrenergic receptors, cAMP, demyelination, axonal degeneration, astrocyte signaling, immune hypothesis, impaired energy metabolism, plasma cells