Apoptosis: a novel therapeutic tool?

S C Dixon1, I N Arah

  • 1Medicine Branch, Clinical Pharmacokinetics Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. nemra@box-n.nih.gov

Insights

Apoptosis, or programmed cell death, is vital for health. Restoring the balance between cell death and proliferation, potentially with genetic approaches, offers new therapeutic strategies for diseases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Apoptosis is a fundamental, genetically programmed cell death process essential for multicellular organism homeostasis.
  • Disruptions in the balance between cell proliferation and apoptosis are implicated in various diseases.
  • Understanding apoptosis pathways is crucial for developing targeted disease therapies.

Purpose of the Study:

  • To explore the molecular mechanisms of apoptosis.
  • To identify potential therapeutic interventions for diseases involving apoptosis dysregulation.
  • To investigate the efficacy and safety of genetic approaches in modulating apoptosis.

Main Methods:

  • Analysis of molecular mechanisms underlying apoptosis.
  • Review of existing therapeutic agents (chemo-, radio-, cytokine therapy).
  • Evaluation of novel genetic approaches in in vitro and animal models.

Main Results:

  • Detailed understanding of apoptosis molecular pathways has emerged.
  • Current therapies show partial success, with remaining challenges in drug-resistant cells.
  • Genetic interventions demonstrate significant success in preclinical models with low toxicity.

Conclusions:

  • Restoring the equilibrium between cell proliferation and death is a key therapeutic goal.
  • Genetic approaches offer a promising, low-toxicity strategy to enhance existing therapies.
  • Combining traditional treatments with genetic interventions may significantly improve therapeutic efficacy and reduce resistance.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

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Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.