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The Role of TRAIL in Human Health and Metabolic Disorders
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The Role of TRAIL in Human Health and Metabolic Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 7760

Special Issue Editor

Dr. Barbara Toffoli

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Guest Editor
Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
Interests: hepatic steatosis; diabetes and its complications; obesity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) is a widely expressed protein belonging to the TNF superfamily. In addition to its well-known apoptotic effect in transformed cells, TRAIL possesses the intriguing ability to spare normal ones. Binding of TRAIL to its death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) leads to the formation of the death-inducing signaling complex (DISC), which in turn triggers a caspase cascade, resulting in cell apoptosis. In addition to DRs, TRAIL can also bind two decoy receptors and soluble OPG, making TRAIL biology multifaceted. In this view, it has been shown that TRAIL could mediate alternative cell death pathways, such as necroptosis and autophagy, as well as survival/proliferation pathways, involving NF-κB, ERK1/2, and Akt signaling.

TRAIL has been widely studied for its promising anticancer effect, and some TRAIL-based monotherapies and combination therapies have reached phase II and phase III clinical trials in humans. Interestingly, recent in vitro and in vivo findings point at new therapeutic possibilities of TRAIL treatments also against systemic inflammation, Type 2 diabetes mellitus, and metabolic disturbances.

This Special Issue aims to present a collection of articles related to the role of TRAIL in human health and various diseases, including cancer, inflammation, obesity, and diabetes. Original research and review articles are welcome.

Dr. Barbara Toffoli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (2 papers)

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Review

17 pages, 1966 KiB  
Review
The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases
by Elaina Kelland, Manisha S. Patil, Sanjay Patel, Siân P. Cartland and Mary M. Kavurma
Int. J. Mol. Sci. 2023, 24(7), 6725; https://doi.org/10.3390/ijms24076725 - 4 Apr 2023
Cited by 6 | Viewed by 2443
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) was originally discovered, almost 20 years ago, for its ability to kill cancer cells. More recent evidence has described pleiotropic functions, particularly in the cardiovascular system. There is potential for TRAIL concentrations in the circulation to act as prognostic [...] Read more.
TNF-related apoptosis-inducing ligand (TRAIL) was originally discovered, almost 20 years ago, for its ability to kill cancer cells. More recent evidence has described pleiotropic functions, particularly in the cardiovascular system. There is potential for TRAIL concentrations in the circulation to act as prognostic and/or diagnostic factors for cardiovascular diseases (CVD). Pre-clinical studies also describe the therapeutic capacity for TRAIL signals, particularly in the context of atherosclerotic disease and diseases of the myocardium. Because diabetes mellitus significantly contributes to the progression and pathogenesis of CVDs, in this review we highlight recent evidence for the prognostic, diagnostic, and therapeutic potential of TRAIL signals in CVDs, and where relevant, the impact of diabetes mellitus. A greater understanding of how TRAIL signals regulate cardiovascular protection and pathology may offer new diagnostic and therapeutic avenues for patients suffering from CVDs. Full article
(This article belongs to the Special Issue The Role of TRAIL in Human Health and Metabolic Disorders)
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21 pages, 1632 KiB  
Review
Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence
by Chrysi Koliaki and Nicholas Katsilambros
Int. J. Mol. Sci. 2022, 23(6), 3225; https://doi.org/10.3390/ijms23063225 - 17 Mar 2022
Cited by 20 | Viewed by 4237
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied [...] Read more.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease. Full article
(This article belongs to the Special Issue The Role of TRAIL in Human Health and Metabolic Disorders)
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