Abstract
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.
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Acknowledgments
Support for this research was provided by the National Institutes for Health grants P01 DA028555, R01 NS036126, P01 NS031492 2R01 NS034239, P01 MH064570, P01 NS043985, P30 MH062261 and R01 AG043540 to H.E.G.; R21 NS049264, R01 NS070190 to R.L.M.; DOD Grant 421-20-09A to H.E.G.; separate grants from the Michael J. Fox Foundation to H.E.G. and to R.L.M.; and in part by the University of Nebraska Foundation which includes individual donations from Carol Swarts, Frances and Louie Blumkin, and the Vice Chancellor’s office of the University of Nebraska Medical Center for Core Facility Developments. We gratefully acknowledge the work of Ashley Reynolds, MD, PhD, and David K. Stone MD, PhD for their authoritative input and work as authors of the first edition version of this chapter.
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Schutt, C., Gendelman, H.E., Mosley, R.L. (2017). Immunotherapies for Movement Disorders: Parkinson’s Disease and Amyotrophic Lateral Sclerosis. In: Ikezu, T., Gendelman, H. (eds) Neuroimmune Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-44022-4_46
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