Cytokines in Neurodegenerative Disorders

The pathogenesis of different neuroinflammatory and neurodegenerative diseases like multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis is associated with elevated production of different proinflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, etc.) within the central nervous system (CNS). It is found that resident glial cells in the CNS (microglia and astrocytes) produce high levels of proinflammatory cytokines in response to a wide variety of proinflammatory and neurodegenerative stimuli. Although pathways leading to the expression of different proinflammatory cytokines may vary in microglia and astrocytes, various signaling cascades are found to come together to activate several transcription factors for the transcription of proinflammatory cytokine genes in glial cells. Once produced in excess, proinflammatory cytokines cause nitrosative, oxidative, and inflammatory stress within the CNS leading to the loss of neurons and myelin-synthesizing oligodendrocytes. Here, we attempt to delineate our current familiarity with signaling mechanisms for the induction of proinflammatory cytokines in glial cells in response to neurodegenerative stimuli and how these proinflammatory cytokines may be involved in the disease process of neurodegenerative disorders. Such understanding may be helpful for possible intervention of neuroinflammation-mediated neurodegenerative disorders.