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Programmed cell death: the influence of CD40, CD95 (Fas or Apo-I) and their ligands
1Immune and Gene Therapy Laboratory, Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. nongnit.lewin@cck.ki.se
Abstract:
Programmed cell death (PCD) or apoptosis is a process whereby developmental or environmental stimuli activate a specific series of events that culminate in cell death. PCD is essential for normal development and abnormality in the process can lead to defects ranging from embryonic lethality and tissue-specific perturbation of postnatal development to a high susceptibility to malignancy. Therapeutics that modulate the regulation of PCD may provide a new opportunity for the treatment of the PCD related diseases and cancer. CD40 and CD95 (Fas/Apo-I) are transmembrane proteins of the nerve growth factor/tumour necrosis factor alpha receptor superfamily. The death signal of PCD occurs when the CD95 receptor on the cell surface binds to the CD95 ligand (CD95L) or to the anti-CD95 monoclonal antibody (mAb). In contrast, PCD could be inhibited by the survival signal mediated from the binding of the CD40 receptor to the CD40 ligand (CD40L) or to the anti-CD40 mAb. In this review, the interaction of CD40/CD40L and CD95/CD95L on PCD in normal and malignant cells is discussed.
Insights
Programmed cell death (PCD) is vital for development, and its dysregulation causes diseases and cancer. Modulating CD40 and CD95 pathways offers therapeutic potential for PCD-related conditions and malignancies.
Area of Science:
- Cell Biology
- Immunology
- Oncology
Background:
- Programmed cell death (PCD), or apoptosis, is a crucial biological process regulated by specific molecular events.
- Aberrations in PCD are linked to developmental defects, postnatal issues, and increased cancer susceptibility.
- CD40 and CD95 are key transmembrane receptors involved in PCD regulation.
Purpose of the Study:
- To review the roles of CD40/CD40L and CD95/CD95L interactions in programmed cell death.
- To explore the implications of these interactions in both normal and malignant cells.
- To highlight the therapeutic potential of modulating PCD pathways.
Main Methods:
- Literature review focusing on CD40 and CD95 signaling pathways.
- Analysis of studies investigating PCD in normal and cancerous cell types.
- Discussion of monoclonal antibody (mAb) and ligand-mediated signaling.
Main Results:
- CD95 receptor activation by CD95 ligand (CD95L) or anti-CD95 mAb initiates PCD.
- CD40 receptor activation by CD40 ligand (CD40L) or anti-CD40 mAb inhibits PCD, promoting cell survival.
- Differential roles of CD40 and CD95 signaling observed in normal versus malignant cells.
Conclusions:
- The interplay between CD40/CD40L and CD95/CD95L pathways significantly influences PCD.
- Targeting these pathways presents a promising strategy for treating PCD-related diseases and cancers.
- Further research into these interactions could lead to novel therapeutic interventions.