Role of Immunity and Inflammation in the Pathophysiology of Neurodegenerative Diseases

Neurodegenerative diseases are the result of progressive loss of neurons and axons in the central nervous system (CNS), which can lead to cognition and motor dysfunction. It is well known that CNS inflammation and immune activation play a major role in the pathophysiology of neurodegenerative diseases. Although the blood-brain barrier (BBB) is able to protect the CNS from immune activation, it becomes more permeable during inflammation, which renders the brain vulnerable to infections. A better understanding of the interaction between inflammatory mediators, such as cytokines, and the activated immune response, including astrocytes and microglia, is critical for the development of new therapeutic strategies for neurodegenerative diseases. This review first describes the role of innate immune activation in neurodegenerative diseases and illustrates the factors that contribute to the communication between the CNS and the immune system. A closer look is given at the role of the BBB in inflammation and immunity, as well as at the animal models used to study inflammation in neurodegenerative diseases. Finally, this review outlines the key pathways and biological mechanisms involved in CNS diseases, with a particular focus on multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). (C) 2015 S. Karger AG, Basel