Autoantibodies and neurodegeneration in multiple sclerosis

Neurodegeneration develops in association with inflammation and demyelination in multiple sclerosis. Available data suggest that the progressive neuroaxonal loss begins in the earliest stages of the disease and underlies the accumulation of clinical disability. The loss of neurons and their processes is driven by a complex molecular mechanism involving cellular and humoral immune histotoxicity, demyelination, reduced neurotrophic support, metabolic impairment, and altered intracellular processes. Here we survey available data concerning the role of autoreactive immunoglobulins in neurotoxicity. A better understanding of molecular pathways leading to immune-mediated neurodegeneration may have key importance in the successful treatment of the disease.