The role of immune processes in amyotrophic lateral sclerosis pathogenesis.
Despite many efforts, the etiopathogenesis of ALS remains unknown. During the last decade evidence for an autoimmune involvement in motoneuron degeneration and death has remarkably increased. Multiple reports have documented significant expression of proteins associated with immune function in affected areas of ALS patients. Two animal models of immune-mediated motoneuron destruction have been developed that closely resemble clinical, electrophysiological and morphological features of human ALS. Inflammatory foci within the spinal cord, and IgG at the neuromuscular junction as well as within upper and lower motoneurons found in the animal models support the role of autoimmune mechanisms of motoneuron destruction in this model. IgG from ALS patients and from the animal models can passively transfer physiological changes at the neuromuscular junction in mice. That ALS IgG interact with calcium channels and induce an alteration of their function is now electrophysiologically and biochemically evident. Furthermore, it has been documented that motoneurons may be selectively vulnerable since they have a deficient calcium buffering capacity. Although further research efforts are necessary to elucidate the interaction of the ALS antibodies with the calcium channel function and how defective calcium handling by the motoneurons is important in their degeneration, the current data strongly suggest the involvement of autoimmune mechanisms in ALS etiopathogenesis.
Alexianu
M E
ME
Institute of Neurology and Psychiatry Bucharest, Romania.
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000276:immunology*; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology*; D015220:Calcium Channels / Q000097:blood; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G; D051379:Mice; D009046:Motor Neurons / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology
D015220:Calcium Channels; D007074:Immunoglobulin G