The AKT axis as a therapeutic target in autoimmune diseases.
Autoimmunity affects a substantial fraction of our population. In patients with autoimmune disease, the immune system recognizes self-tissues as foreign. Common autoimmune diseases include rheumatoid arthritis, diabetes mellitus, lupus and multiple sclerosis. Though different target organs may be affected in different autoimmune diseases, aberrations in adaptive or innate immunity underlie all of these diseases. Abnormal functioning, differentiation and/or activation of T-cells, B-cells and myeloid cells have been documented in various autoimmune diseases. More recent studies have also detailed anomalous activation of various signaling axes including various MAPK, AKT, NF-kappaB, Bcl-2 family members, and JAK/STAT molecules in these cells, in the context of systemic autoimmunity. Among these, one molecular pathway that appears to be particularly attractive for therapeutic targeting is the PI3K/AKT/mTOR axis. In this review, we summarize how the AKT axis affects multiple molecular processes in autoimmune diseases and discuss the potential of targeting this axis in these diseases.
Wu
Tianfu
T
Department of Internal Medicine (Rheumatology), University of Texas Southwestern Medical School, Dallas, TX 75390-8884, USA. Tianfu.wu@utsouthwestern.edu
Mohan
Chandra
C
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000209:etiology; D049109:Cell Proliferation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000209:etiology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction
D051057:Proto-Oncogene Proteins c-akt