Neuroinflammation in Neurodegenerative Disorders: Harmful or Helpful?

Abstract

Alzheimer's, Parkinson's, and Lou Gehrig's diseases are neurodegenerative disorders affecting at least 6 million people in the U.S. alone. Despite their prevalence, the forces driving disease onset and progression are poorly understood. This makes clear diagnoses difficult and limits treatments to symptomatic relief. A mere fraction of cases have a known genetic cause; most are "sporadic," or of unknown origin. However, striking commonalities emerge: changes in inflammation, microglia and T cell populations, as well as levels and localization of immune proteins. These changes constitude evidence of immune alteration, which is commonly thought to slow disease progression by clearing harmful protein aggregates and dead neurons. However, inappropriate immune activation may promote neuronal loss through autoimmunity or other methods. Developing cures, treatments, and preventions requires a more complete understanding of the underlying molecular and cellular mechanisms. A critical step towards understanding these underpinnings is elucidating the immune system's potential roles. In this thesis, I consider evidence the immune system may play a protective or harmful role in three neurodegenerative disorders: Alzheimer's, Parkinson's, and Lou Gehrig's diseases. I also discuss the potential for immunotherapies to treat these disorders. Together, the evidence suggests unexpected roles for immune cells and proteins in neurodegenerative disorders, and novel approaches towards diagnosis, treatment, and prevention.