Protective and regenerative autoimmunity in CNS injury

Neurodegenerative diseases are generally considered to be non-inflammatory, unlike autoimmune diseases such as multiple sclerosis, which are neurodegenerative diseases that are inflammatory in nature (Trapp et al., 1999a, b; Hohlfeld and Wiendl, 2001; Groom et al., 2003). Nevertheless, most neurodegenerative diseases are accompanied by a local inflammatory response, widely assumed to be unfavorable for CNS recovery (Kurosinski and Gotz, 2002; Jellinger, 2003; Popovich and Jones, 2003). Moreover, the progressive degeneration seen in such diseases is often mediated by compounds and processes that are secondary to the primary risk, e.g., misfolding and aggregation of self-proteins (Shastry, 2003). These primary and secondary risk factors represent a continuous threat to any viable neurons embedded in a chronically diseased tissue; they induce abnormalities in cells in their vicinity, thereby contributing to the chaos rather than helping to resolve it.