Cellular and Molecular Biology
Open Access

Cell Death; Apoptosis; Cells; Biological

Introduction

Understanding apoptosis

Apoptosis is a highly orchestrated and controlled process that involves a series of biochemical events leading to the orderly selfdestruction of a cell. It is characterized by distinct morphological and molecular changes, including cell shrinkage, chromatin condensation, nuclear fragmentation, membrane blebbing, and the formation of apoptotic bodies. Unlike necrosis, another form of cell death associated with cellular damage and inflammation, apoptosis is an energydependent process that does not elicit an immune response [1].

The importance of apoptosis in physiology

Apoptosis is essential for various physiological processes, such as embryogenesis, tissue development, and immune system regulation. During embryonic development, apoptosis plays a critical role in shaping tissues and organs by eliminating cells that are no longer needed or have become redundant. It also helps to sculpt complex structures like fingers and toes by removing the webbing between them. In adult organisms, apoptosis is vital for maintaining tissue homeostasis and eliminating aged or damaged cells. For example, in the immune system, apoptosis is involved in the elimination of self-reactive immune cells to prevent autoimmune disorders. It also plays a crucial role in the removal of cells infected with viruses or other pathogens, thereby contributing to the body's defense against infections [2].

Apoptosis and disease

Dysregulation of apoptosis has been implicated in a wide range of diseases, including cancer, neurodegenerative disorders, autoimmune diseases, and cardiovascular diseases. In cancer, the ability of cells to evade apoptosis is one of the hallmarks of malignancy. Cancer cells often acquire mutations that disrupt the apoptotic machinery, allowing them to survive and proliferate uncontrollably. Developing therapeutic strategies that restore apoptosis in cancer cells has been a major focus of cancer research.

Neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by the progressive loss of neurons. Apoptosis has been identified as a major contributor to neuronal death in these conditions. Understanding the apoptotic pathways involved in neurodegeneration can potentially lead to the development of novel therapies aimed at preventing or slowing down the disease progression.

In autoimmune diseases, faulty regulation of apoptosis can result in the accumulation of self-reactive immune cells, leading to tissue damage. For example, in Systemic Lupus Erythematosus (SLE), increased resistance to apoptosis in immune cells contributes to the development of autoantibodies and the destruction of healthy tissues [3].

Therapeutic implications of apoptosis

Given the significance of apoptosis in various diseases, targeting apoptotic pathways has emerged as a promising therapeutic approach. Apoptosis-inducing therapies have been investigated as potential cancer treatments. By selectively triggering apoptosis in cancer cells, these therapies aim to eliminate malignant cells while sparing healthy tissues. Several drugs that promote apoptosis, such as BH3 mimetics, are currently being evaluated in clinical trials and show promising results in different types of cancer [4].

On the other hand, therapies aimed at inhibiting apoptosis are being explored for conditions in which excessive cell death occurs. In neurodegenerative diseases, researchers are investigating strategies to prevent neuronal apoptosis or enhance neuronal survival. The development of drugs that target specific apoptotic pathways or molecules involved in the regulation of apoptosis may offer [5].

Discussion

Cell death: Apoptosis

Apoptosis, also known as programmed cell death, is a fundamental biological process that plays a crucial role in various physiological and pathological conditions. It is a tightly regulated process that allows for the removal of unwanted or damaged cells, maintaining tissue homeostasis, and eliminating potentially harmful cells. Understanding the mechanisms underlying apoptosis is essential for gaining insights into various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases [6].

One of the key features of apoptosis is its highly controlled nature. It involves a series of well-orchestrated events that are initiated and executed by a cascade of intracellular signaling pathways. These pathways are regulated by both extrinsic and intrinsic factors, ensuring a fine balance between cell survival and death. Extrinsic factors, such as cytokines and growth factors, can activate cell surface receptors, leading to the activation of specific signaling pathways that ultimately result in apoptosis. Intrinsic factors, on the other hand, can be triggered by cellular stressors, DNA damage, or the activation of specific genes, which initiate a cascade of events leading to cell death [7].

The molecular machinery involved in apoptosis is complex and involves the participation of various proteins. One of the key players in apoptosis is the Bcl-2 family of proteins, which includes both proapoptotic and anti-apoptotic members. The balance between these two groups of proteins determines the fate of the cell. For instance, pro-apoptotic members, such as Bax and Bak, promote cell death by inducing mitochondrial outer membrane permeabilization, while anti-apoptotic members, such as Bcl-2 and Bcl-xL, prevent cell death by inhibiting the actions of pro-apoptotic proteins. Disruption of this balance can lead to abnormal cell survival or excessive cell death, contributing to disease development [8].

Another important component of apoptosis is the activation of caspases, a family of proteases that play a central role in executing cell death. Caspases are present as inactive zymogens in the cell, and their activation is tightly regulated. Initiator caspases, such as caspase-8 and caspase-9, are activated in response to specific signals and subsequently activate effector caspases, such as caspase-3 and caspase-7. Effector caspases cleave a variety of cellular substrates, leading to the characteristic morphological and biochemical changes observed in apoptotic cells, including DNA fragmentation, chromatin condensation, and membrane blebbing [9].

Apoptosis has significant implications in human health and disease. Dysregulation of apoptosis can contribute to the development and progression of various disorders. For example, defects in apoptosis can lead to the accumulation of damaged cells, promoting the development of cancer. Conversely, excessive apoptosis can result in tissue damage and organ dysfunction, as observed in neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Furthermore, dysregulated apoptosis can also contribute to autoimmune diseases, where selfreactive immune cells are not efficiently eliminated [10].

Conclusion

Apoptosis, or programmed cell death, is a highly regulated biological process that is essential for maintaining tissue homeostasis and eliminating unwanted or damaged cells. It involves a complex cascade of intracellular signaling pathways and the participation of numerous proteins, such as the Bcl-2 family and caspases. The balance between pro-apoptotic and anti-apoptotic factors determines the fate of the cell, and dysregulation of apoptosis can contribute to the development and progression of various diseases. Understanding the mechanisms underlying apoptosis is of great importance for the development of therapeutic strategies targeting diseases characterized by abnormal cell death or survival. Manipulating apoptotic pathways can potentially provide new approaches for cancer treatment, where enhancing apoptosis in cancer cells while sparing normal cells is a promising therapeutic goal.

Acknowledgement

None

Conflict of Interest

None

1. Josson S, Xu Y, Fang F, Dhar S, St Clair D, et al. (2006) RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells. Oncogene 25: 1554-1559.

Google Scholar, Crossref, Indexed at         

2. Yu J, Sun L, Hao T, Zhang B, Chen X, et al. (2019) Restoration of FKBP51 protein promotes the progression of castration resistant prostate cancer. Ann Transl Med 7: 729.

Google Scholar, Crossref, Indexed at         

3. Liu Y, Jiang J, Liu C, Zhao W, Ma Y, et al. (2021) Synergistic anti-tumor effect of anti-PD-L1 antibody cationic microbubbles for delivery of the miR-34a gene combined with ultrasound on cervical carcinoma. Am J Transl Res 13: 988-1005.

Google Scholar, Indexed at                      

4. Díaz de la Guardia-Bolívar E, Barrios-Rodríguez R, Zwir I, Jiménez-Moleón J, Del Val C (2022) Identification of novel prostate cancer genes in patients stratified by Gleason classification: role of antitumoral genes. Int J Cancer.

Indexed at, Google Scholar, Crossref

5. Wang B, Liu D, Guo Q, Han X, Bi X, et al. (2020) NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression. Cancer Manag Res 12: 3069-3078.

Google Scholar, Crossref, Indexed at        

6. Gennarino V, Alcott C, Chen C, Chaudhury A, Gillentine M, et al. (2015) NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation. Elife 4: e10782.

Google Scholar, Crossref, Indexed at         

7. Chu Y, Elrod N, Wang C, Li L, Chen T, et al. (2019) Nudt21 regulates the alternative polyadenylation of Pak1 and is predictive in the prognosis of glioblastoma patients. Oncogene 38: 4154-4168.

Google Scholar, Crossref, Indexed at         

8. Brumbaugh J, Di Stefano B, Wang X, Borkent M, Forouzmand E, et al. (2018) Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling. Cell 172: 106-120.

Google Scholar, Crossref, Indexed at         

9. Tan S, Li H, Zhang W, Shao Y, Liu Y, et al. (2018) NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression. Oncogene 37: 4887-4900.

Google Scholar, Crossref, Indexed at         

10. Szczepanek J, Styczyński J, Tretyn A, Pogorzała M, Wysocki M (2012) Identification of the genes expression profile associated with the ex vivo resistance to etoposide in childhood acute leukemias. Postepy Hig Med Doswy 66: 401-408.

Google Scholar, Crossref, Indexed at