Abstract
The loss of vital cells within healthy tissues contributes to the development, progression and treatment outcomes of many human disorders, including neurological and infectious diseases as well as environmental and medical toxicities. Conversely, the abnormal survival and accumulation of damaged or superfluous cells drive prominent human pathologies such as cancers and autoimmune diseases. Apoptosis is an evolutionarily conserved cell death pathway that is responsible for the programmed culling of cells during normal eukaryotic development and maintenance of organismal homeostasis. This pathway is controlled by the BCL-2 family of proteins, which contains both pro-apoptotic and pro-survival members that balance the decision between cellular life and death. Recent insights into the dynamic interactions between BCL-2 family proteins and how they control apoptotic cell death in healthy and diseased cells have uncovered novel opportunities for therapeutic intervention. Importantly, the development of both positive and negative small-molecule modulators of apoptosis is now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.
Keywords
ApoptosisProgrammed cell deathBiologyBcl-2 familyNeurodegenerationCell biologyDiseaseHomeostasisCaspaseImmunologyCancer researchMedicineGeneticsInternal medicine
MeSH Terms
AnimalsApoptosisDiseaseHomeostasisHumansNeoplasmsPathologyProto-Oncogene Proteins c-bcl-2
Affiliated Institutions
Related Publications
Involvement of Caspases in Neutrophil Apoptosis: Regulation by Reactive Oxygen Species
Abstract Human neutrophils have a short half-life and are believed to die by apoptosis or programmed cell death both in vivo and in vitro. We found that caspases are activated i...
bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages.
Neutrophils, the most common inflammatory leukocytes, have the most limited life span of all blood cells. After they undergo apoptosis, they are recognized and engulfed by macro...
Hematopoietic Stem Cells Need Two Signals to Prevent Apoptosis; Bcl-2 Can Provide One of These, Kitl/C-KIT Signaling the Other
Growth factors can cause cells to proliferate, differentiate, survive, or die. Distinguishing between these responses is difficult in multicellular, multiparameter systems. Yet ...
Tumor necrosis factor α induces a caspase-independent death pathway in human neutrophils
Tumor necrosis factor α (TNF-α) is a cytokine with multiple roles in the immune system, including the induction and potentiation of cellular functions in neutrophils (PMNs). TNF...
Publication Info
- Year
- 2019
- Type
- review
- Volume
- 20
- Issue
- 3
- Pages
- 175-193
- Citations
- 1923
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
1923
OpenAlex
54
Influential
Cite This
Rumani Singh,
Anthony Letai,
Kristopher A. Sarosiek
(2019).
Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins.
Nature Reviews Molecular Cell Biology
, 20
(3)
, 175-193.
https://doi.org/10.1038/s41580-018-0089-8
Identifiers
- DOI
- 10.1038/s41580-018-0089-8
- PMID
- 30655609
- PMCID
- PMC7325303