Involvement of Fc Receptors in Disorders of the Central Nervous System

Immunoglobulins are proteins with a highly variable antigen-binding domain and a constant region (Fc domain) that binds to a cell surface receptor (FcR). Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells) triggers effector responses including cytokine production, phagocytosis, and degranulation. In addition to their roles in normal responses to infection or tissue injury, and in immune-related diseases, FcRs are increasingly recognized for their involvement in neurological disorders. One or more FcRs are expressed in microglia, astrocytes, oligodendrocytes, and neurons. Aberrant activation of FcRs in such neural cells may contribute to the pathogenesis of major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ischemic stroke, and multiple sclerosis. On the other hand, FcRs may play beneficial roles in counteracting pathological processes; for e.g., FcRs may facilitate removal of amyloid peptides from the brain and so protect against Alzheimer's disease. Knowledge of the functions of FcRs in the nervous system in health and disease is leading to novel preventative and therapeutic strategies for stroke, Alzheimer's disease, and other neurological disorders.