Abstract
The TNF-related apoptosis inducing ligand TRAIL is a member of the TNF superfamily that has been firstly studied and evaluated for its anti-cancer activity, and the insights into its biology have already led to the identification of several TRAIL-based anticancer strategies with strong clinical therapeutic potentials. Nonetheless, the TRAIL system is far more complex and it can lead to a wider range of biological effects other than the ability of inducing apoptosis in cancer cells. By virtue of the different receptors and the different signalling pathways involved, TRAIL plays indeed a role in the regulation of different processes of the innate and adaptive immune system and this feature makes it an intriguing molecule under consideration in the development/progression/treatment of several immunological disorders. In this context, central nervous system represents a peculiar anatomic site where, despite its “status” of immune-privileged site, both innate and adaptive inflammatory responses occur and are involved in several pathological conditions. A number of studies have evaluated the role of TRAIL and of TRAIL-related pathways as pro-inflammatory or protective stimuli, depending on the specific pathological condition, confirming a twofold nature of this molecule. In this light, the aim of this review is to summarize the main preclinical evidences of the potential/involvement of TRAIL molecule and TRAIL pathways for the treatment of central nervous system disorders and the key suggestions coming from their assessment in preclinical models as proof of concept for future clinical studies.
Highlights
The acronym TRAIL designates a member of the tumor necrosis factor (TNF) family first reported in the 1990s by two independent studies
The TNF-related apoptosis inducing ligand TRAIL is a member of the TNF superfamily that has been firstly studied and evaluated for its anti-cancer activity, and the insights into its biology have already led to the identification of several TRAIL-based anticancer strategies with strong clinical therapeutic potentials
We have shown that low levels of TRAIL are associated with total and cardiovascular mortality in older adults and interestingly, we have demonstrated that 17-b estradiol could play a role in regulating the amount of TRAIL in circulation by mediating downregulation of TRAIL expression [8, 9]
Summary
Veronica Tisato1 • Arianna Gonelli1 • Rebecca Voltan1 • Paola Secchiero1 • Giorgio Zauli1 Received: 17 November 2015 / Revised: 8 February 2016 / Accepted: 9 February 2016 / Published online: 24 February 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com
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