Protein-based therapeutic approaches targeting death receptors
Details
Serval ID
serval:BIB_C64A159D235E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Protein-based therapeutic approaches targeting death receptors
Journal
Cell Death and Differentiation
ISSN
1350-9047 (Print)
Publication state
Published
Issued date
01/2003
Volume
10
Number
1
Pages
117-23
Notes
Journal Article
Review --- Old month value: Jan
Review --- Old month value: Jan
Abstract
Death receptors (DRs) are a growing family of transmembrane proteins that can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. Eight human DRs (Fas, TNF-R1, TRAMP, TRAIL-R1, TRAIL-R2, DR-6, EDA-R and NGF-R) have been identified. The best studied to date is Fas (CD95). Expression and signaling by Fas and its ligand (FasL, CD95L) is a tightly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homeostasis. Recently, strong evidence has shown that dysregulation of Fas expression and/or signaling contributes to the pathogenesis of tissue destructive diseases such as graft-versus-host disease, toxic epidermal necrolysis, multiple sclerosis and stroke. With these new developments, strategies for modulating the function of Fas signaling have emerged and provided novel protein-based therapeutic possibilities that will be discussed herein. Selective triggering of DR-mediated apoptosis in cancer cells is an emerging approach that is being intensely investigated as a mode of cancer therapy. Local administration of Fas agonists, and more promisingly, systemic use of soluble recombinant forms of TRAIL have shown efficacy in preclinical models of the disease. Developments in this field that may have important clinical implications for the treatment of cancer are reviewed.
Keywords
Animals
Antigens, CD95/*drug effects/metabolism
Antineoplastic Agents/therapeutic use
Apoptosis/*drug effects/physiology
Apoptosis Regulatory Proteins
Eukaryotic Cells/*drug effects/metabolism
Fas Ligand Protein
Humans
Membrane Glycoproteins/*agonists/therapeutic use
Neoplasms/*drug therapy/genetics/metabolism
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha/therapeutic use
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:19
Last modification date
20/08/2019 15:41