title: 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.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44121, Ferrara, Italy. veronica.tisato@unife.it.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tisato
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44121, Ferrara, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Gonelli
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44121, Ferrara, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Voltan
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44121, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44121, Ferrara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology; D002470:Cell Survival; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D003072:Cognition Disorders / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000503:physiopathology; D009369:Neoplasms / Q000503:physiopathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D015398:Signal Transduction; D020521:Stroke / Q000503:physiopathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
chemical_list: D015415:Biomarkers; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
keywords: Alzheimer’s disease; Biomarker; Ischemic stroke; Multiple sclerosis; Neuroinflammation; TRAIL; Therapeutic potential