The Role of Clearance in Neurodegenerative Diseases

Abstract

The immune system plays early and important inflammatory roles in the pathophysiology of diverse neurodegenerative disorders. This inflammation is not restricted to the central nervous system (CNS) in neurodegenerative diseases, but is also expressed systemically. In fact, peripheral immune alterations and inflammation augment disease burden and rates of disease progression. Thus neurodegeneration is a multifactorial, multisystem syndrome in which the CNS and peripheral immune systems play important roles in development and progression of disease. Inflammation was previously considered the consequence and not the cause of neuronal injury. However, more recent evidence suggests that the immune system actively contributes to neuroprotection at early phases of disease and contributes to neurotoxicity in later phases of disease. Neuronal injury is non-cell-autonomous and depends on well-orchestrated dialogues between peripheral and CNS immune systems, glia, and neurons. This chapter will review the proposed mechanisms of inflammation 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 manipulating microglial and lymphocytic functions has the potential to ameliorate devastating neurodegenerative disorders.