The role of TRAIL/TRAIL receptors in central nervous system pathology

Item Type:	Article
Title:	The role of TRAIL/TRAIL receptors in central nervous system pathology
Creators Name:	Aktas, O. and Schulze-Topphoff, U. and Zipp, F.
Abstract:	Initially, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) aroused major interest due to its preferential toxic effect against malignant cells. However, subsequent studies revealed that the TRAIL system, comprising the family of signal-mediating and decoy TRAIL receptors, (i) can also induce death of non-transformed cells, (ii) has potent immunoregulatory functions, and (iii) exhibits a unique expression pattern in the central nervous system (CNS). Indeed, TRAIL is not expressed within the human brain, while apoptosis-inducing TRAIL receptors are found differently distributed on neurons, oligodendrocytes, and astrocytes. These findings rule out a major contribution of TRAIL to the so-called "immune privilege" of the brain, in which local inflammation is limited, although such a role has previously been suggested for the CD95 (Fas) ligand belonging to the same TNF/nerve growth factor (NGF) family. If, under pathologic circumstances, the CNS is inflamed, immune cells such as macrophages and T cells upregulate TRAIL upon activation and use this death ligand as a weapon, not only against tumor cells but also against neurons and oligodendrocytes within the inflamed CNS. In parallel, a profound immunoregulatory impact of TRAIL on activation and proliferation of encephalitogenic T cells outside the brain has also been shown. Thus, these studies have uncovered a complex action of TRAIL on CNS pathology, indicating the possible value of targeted manipulation of the TRAIL system for the treatment of inflammatory neurodegenerative diseases such as multiple sclerosis.
Keywords:	TNF-Related Apoptosis-Inducing Ligand, Receptors, Central Nervous System Diseases
Source:	Frontiers in Bioscience
ISSN:	1093-9946
Publisher:	Frontiers in Bioscience
Volume:	12
Page Range:	2912-2921
Date:	1 May 2007
Official Publication:	https://doi.org/10.2741/2281
PubMed:	View item in PubMed

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