Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation.
In a wide variety of acute and chronic central nervous system (CNS) disorders, inflammatory processes contribute to the damage of brain cells and progression of the disease. Along with other regulatory cytokines, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is involved in the pathology of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE), bacterial meningitis (BM), HIV encephalitis (HIVE), stroke and Alzheimer's disease (AD). In these conditions, TRAIL is released within the brain mainly by activated microglia and leukocytes infiltrating from the blood stream. TRAIL promotes apoptosis of parenchymal cells in MS/EAE, HIVE, AD and stroke through interaction with TRAIL death receptors expressed on these cells. Frequently, cells in the diseased brain display increased susceptibility to apoptosis induction by TRAIL due to upregulation of death receptors and downregulation of decoy receptors. On the other hand, TRAIL inhibits the proliferation of encephalitogenic T cells in EAE, and it is involved in the clearance of infected brain macrophages in HIVE and of activated neutrophils in BM by interaction with their death receptors. Especially in BM, the ability of TRAIL to limit an acute granulocyte-driven inflammation carries significant neuroprotective potential. Given the diversity of beneficial and harmful effects in the immune and nervous system, TRAIL is a double-edged sword in diseases involving CNS inflammation.
Hoffmann
Olaf
O
Department of Neurology, Charité--Universitätsmedizin Berlin, Berlin, Germany.
Zipp
Frauke
F
Weber
Joerg R
JR
D000544:Alzheimer Disease / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology*; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008581:Meningitis / Q000276:immunology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology* / Q000378:metabolism
D053221:TNF-Related Apoptosis-Inducing Ligand