Immunotherapies for movement disorders: Parkinson’S disease and amyotrophic lateral sclerosis

Although patterns of neuronal degeneration are unique in PD and ALS, both disorders share common pathways and processes that support and possibly initiate neurodegeneration. Most of these processes are associated with induction, propagation, or consequences of neuroinflammation. Increased numbers of microglia that express reactive phenotypes and proximate dying neurons reflect the neuroinflammatory cellular response. Neuroinflammation amplifies oxidative stresses via reactive oxygen, nitrogen, and carbon species that react with biomolecules and increase molecular modifications of lipids, proteins, and nucleic acids. These reactive modifications eventually become deleterious to biochemical and cellular processes resulting in dysregulation of cellular functions and further neuronal injury and death. Whether neuroinflammatory responses are causal or consequential remains to be determined. Nevertheless, the importance of inflammatory responses to neurodegeneration is underscored in animal models, whereby attenuation of neuroinflammation by genetic manipulation or pharmacological agents mitigates neurodegeneration and increases neuronal survival. As such, immunological strategies that target neuroinflammatory processes represent promising candidates for therapeutic intervention in neurodegenerative disorders. These strategies embrace the capacity of regulatory T cells to protect neurons either directly via neurotrophic factors, or indirectly by modulation of microglial function to attenuate neuroinflammatory responses and by induction of astrocyte-derived neurotrophic factors.