Role of NF-κB in neurodegenerative diseases

摘要

Besides the constitutively active form of nuclear factor-κB (NF-κB), which is required for neuronal plasticity, inducible activation of this transcription factor in neuronal and glial cells is frequently associated with neurodegenerative diseases. Here, we summarize current findings on the role of NF-κB in initiation, progression, and mitigation of acute or chronic neuropathologies with a special emphasis on subunit- and cell-type-specific effects. We discuss disease-specific functions of NF-κB and draw conclusions with respect to common regulatory mechanisms. A special focus will be on how NF-κB-dependent gene expression becomes critical for neuronal cell fate decision. Macroglial NF-κB activation will be addressed in the context of chronic neurodegeneration, neuroinflammation, and scar formation. Further, the complex role of NF-κB in microglia and immune cells for CNS autoimmune responses and tissue damage is covered. Finally, we will review case reports and studies on transgenic mouse lines to illustrate how mutations in genes encoding constituents of the NF-κB signaling pathway are linked to CNS dysfunction and hereditary mental retardation.