To be or not to be at the cellular level: importance of apoptosis

Apoptosis in cell lifespan

Morphological changes which affect cells include:

• Cell blebbing
• Cell shrinkage
• Nuclear DNA fragmentation
• Chromatin condensation.

The whole process ends by the cell literally eating itself without a trace of inflammation, which is a hallmark of necrosis, a form of non-programmed cell death.

Each day adults lose between 50 and 70 billion cells due to apoptosis, while children lose approximately 20 – 30 billion cells per day.

Apoptosis and disease

It is evident that apoptosis is a highly important biological phenomenon. A defective apoptotic process, either over-activated or supressed, has been implicated in numerous human diseases and disorders, such as:

• Cancer
• Neurological disorders – Alzheimer’s, Parkinson’s, and Huntington’s disease, amyotrophic lateral sclerosis, stroke
• Cardiovascular disorders – ischaemia, heart failure
• Infectious diseases – bacterial, viral
• Autoimmune diseases – systemic lupus erythematosus, autoimmune lymphoproliferative syndrome, rheumatoid arthritis, thyroiditis.

Key apoptotic players

Over 50 years of fundamental research in the field of apoptosis has enabled the discovery of key apoptotic players implicated in the regulation/execution of that process as a warrant to the development of targeted therapeutic strategies.

Molecular targets belong to one of the following categories:

• Caspases
• Cell death receptors
• Bcl-2 proteins
• p53
• IAPs
• SMAC.

Currently, there are several ongoing clinical and preclinical studies which include therapeutic approaches that target at least one key apoptotic player.

One interesting fact is that the induction of apoptosis is a hallmark of SARS-CoV-2 infection; thus, targeting virus-induced apoptosis could be a promising strategy in the treatment of SARS-CoV-2 infection.

Other similar mechanisms

As a former researcher in the field of cell death, I know how challenging it can be to selectively eliminate targeted cells or selectively insure prevention of cell death. Moreover, apoptosis is not the only form of programmed cell death: autophagy, necroptosis, and mitoptosis are some of the other forms of programmed cell death, which are also implicated in the development of human diseases that share the same key players with apoptosis, but sometimes in a different context.

However, if you have resolved the cell-death continuum dilemma, and have at your disposal promising cell-death-based therapeutics, feel free to contact Mart Farm as a reliable partner which will support your product’s life cycle from its development to regulatory compliance.

Maja Antunović, PhD / Medical Writer & Medical Reviewer

References:

1. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY). 2012 May;4(5):330-49. doi: 10.18632/aging.100459. PMID: 22683550; PMCID: PMC3384434.

2. Fischer U, Schulze-Osthoff K. Apoptosis-based therapies and drug targets. Cell Death Differ. 2005 Aug;12 Suppl 1:942-61. doi: 10.1038/sj.cdd.4401556. PMID: 15665817.

3. Donia A, Bokhari H. Apoptosis induced by SARS-CoV-2: can we target it? Apoptosis. 2021 Feb;26(1-2):7-8. doi: 10.1007/s10495-021-01656-2. Epub 2021 Jan 29. PMID: 33512610; PMCID: PMC7844099.