Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral sclerosis and other neurodegenerative disorders

Neurodegenerative diseases, Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis (ALS) are progressive and devastating disorders of the nervous system without cure. Although a number of distinct, but not mutually exclusive, mechanisms can affect disease pathogenesis, neuroinflammation stands in common. It commonly occurs as a consequence of oxidative and excitotoxic neuronal damage, mitochondrial dysfunction and protein aggregation. Thus, it is believed drugs that modulate inflammation may combat disease progression. Such strategies include those commented on in this report by Arie Neymotin, et al. demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin, et al., 2009). While anti-inflammatory interventions may be required, they may not be sufficient, to positively affect clinical outcomes. The targeting of combinations of pathogenic events including clearance of disaggregated proteins together with neuroprotective and immune modulatory strategies may all be required to facilitate positive disease outcomes. This may include the targeting of both innate and adaptive neurotoxic immune responses. The commentary is designed to summarize the promises and perils in achieving immunoregulation for brain homeostatic responses and inevitable therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are discussed with a particular focus on ALS. Copyright © 2009. Published by Elsevier Inc.