Therapeutic approaches to the treatment of neuroinflammatory diseases.
Microglia cells are present in the central nervous system and respond quickly to pathogenic stimuli in order to protect the brain. When these immunological responses activate inappropriately or are prolonged, they can contribute to the neuronal damage observed in many neurodegenerative diseases. A variety of immune system modulators including complement proteins, inflammatory cytokines such IL-1 alpha, IL-1 beta, IL-3, IL-6, TNF-alpha, and S100 beta, colony-stimulating factor-1, coagulation proteins and matrix metalloproteases are made by both microglia and astrocytes. Additionally astrocytes, the predominant glial component of the brain, express cell-adhesion molecules, cytokine receptors and induce nitric oxide synthease. The pathophysiology of Alzheimer's disease, stroke, traumatic brain injury, and multiple sclerosis suggest that a large portion of the irreversible damage observed can be attributed to a neuroinflammatory mechanism. The immunomodulators of these diseases are reviewed and new agents within specific molecular mechanisms are presented and discussed.
Hays
S J
SJ
Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D001921:Brain / Q000502:physiology; D002490:Central Nervous System / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000473:pathology; D016207:Cytokines / Q000502:physiology; D007154:Immune System Diseases / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy*; D015394:Molecular Structure; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology*; D009457:Neuroglia / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D016207:Cytokines