Authors: Pearl-Yafe, Michal; Kaminitz, Ayelet; Yolcu, Esma S.; Yaniv, Isaac; Stein, Jerry; Askenasy, Nadir

Source: Current Pharmaceutical Design, Volume 13, Number 7, March 2007 , pp. 749-760(12)

Publisher: Bentham Science Publishers

Abstract:

Abundant information is available on the involvement of various cellular and molecular mechanisms in β cell apoptosis. The experimental evidence is controversial and difficult to reconcile, and the mechanisms of evasion of the autoreactive clones from immune surveillance are poorly understood. Multiple apoptotic pathways play a role in destructive insulitis, including perforin/granzyme, Fas/Fas-ligand (FasL), and other members of the necrosis factor superfamily. These pathways present redundant behaviors in both the initial and late stages of + cell injury, and at the same time, each molecular mechanism is dispensable in the evolution of autoimmune diabetes. There may be a preferential use of perforin/ granzyme in CD8+ T cell-mediated lysis, which participates in onset of autoimmunity, and a predominance of FasL in CD4+ T cell-mediated insulitis. Several cytokines released in the inflammatory infiltrate induce Fas expression in cells, priming them to FasL-mediated apoptosis. In this review, we focus on the possible participation of multiple cell subsets and molecular mechanisms in the pathogenesis of diabetes to the point where inflammation incites an irreversible vicious cycle that perpetuates βcell death.

Keywords: Autoimmune diabetes; βcells; insulitis; T cells; antigen presenting cells; perforin/granzyme; Fas-ligand; tumor necrosis factor

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161207780249155

Publication date: 2007-03-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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