MULTIPLE-SCLEROSIS - AN ALTERED IMMUNE-RESPONSE OR AN ALTERED STRESS-RESPONSE

The pathogenesis of multiple sclerosis (MS), the major neurological di sease of young adults in the Western world, is still poorly understood , and no effective therapy to block MS is available as yet. The clinic al symptoms of MS result from inflammatory damage to the insulating my elin sheath of axons in the CNS and - at later stages - to axons thems elves. A local autoimmune process involving activation of helper T cel ls against CNS protein components is likely to be crucial in this deve lopment. Especially at the first stages of MS, therapies aimed at the selective downregulation of MS-specific autoimmune responses may contr ibute to controlling the disease. Key to the success of such approache s is the identification of CNS proteins that are the target of local T cell responses. We recently identified the small heat-shock protein a lpha B-crystallin as the single immunodominant myelin antigen in MS-af fected myelin. This review discusses the functional and therapeutic im plications of this finding along with other data on MS, and hypothesiz es that an inappropriate stress response within the CNS itself is cruc ial as an initiating event in disease development.