Role of Inflammation in Neurodegenerative Diseases

It is generally accepted that the immune system plays early and important neuroinflammatory roles in the pathophysiology of diverse neurodegenerative disorders. Such inflammation has been considered the consequence and not the cause of neuronal injury, and contributes to the pathology and tissue destruction. However, more recent evidence challenges this belief and suggests that in early phases of disease the immune system actively contributes to neuroprotection; later in disease progression there is an operational transformation and the response of the immune system becomes neurotoxic. Thus, neuronal injury is non-cell-autonomous and depends on a well-orchestrated dialogue between the immune system and neurons. This chapter reviews the proposed mechanisms of neuroinflammation in the context of neuronal protection and injury based on animal models and human disease. The cumulative evidence suggests that inflammation plays a central role in pathology, and manipulation of microglial and lymphocyte functions has the potential to ameliorate neurodegenerative disorders.