Clinical perspectives of TRAIL: insights into central nervous system disorders

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.

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

“…During the last two decades, several groups have addressed the role of TRAIL not only in cancer but also in other non-neoplastic diseases. Along with other Authors, we have found an inverse correlation between circulating TRAIL and the presence or the adverse prognosis of different pathological conditions including cardiovascular disease (CVD), type 1 and type 2 diabetes, and neurological disorders [11][12][13][14][15][16][17][18][19][20][21]. In addition, our results have provided insights into the therapeutic potential of recombinant TRAIL administration [22][23][24][25][26].…”

Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms

“…To test this further, we measured the protein levels of the inflammatory cytokines, IL-6, previously shown to be increased in patients and animal models across several MPS disorders [23][24][25]. We have also measured the levels of TNFSF10 (TRAIL), which has been associated with neuroinflammation in adult neurodegenerative diseases including Alzheimer's disease and multiple sclerosis [26,27]. We found that in the majority of MPS samples, levels of IL-6 and TRAIL proteins showed a trend for an increase.…”

Inflammation and Cardiovascular Cross Talk in Ischemic Vascular Diseases

“…The article of B. Toffoli et al addresses the role of two other cytokines belonging to the TNF family. Osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) are two factors showing controversial effects on several physiopathological contexts [7, 8]. In a preclinical model, the authors show that dyslipidaemia and diabetes, two risk factors for cardiovascular disease, modify the vascular and cardiac expression of OPG and TRAIL leading to an increased OPG/TRAIL ratio.…”