What is caspase mediated cell death?
The caspase family is well characterized as playing a crucial role in modulation of programmed cell death (PCD), which is a genetically regulated, evolutionarily conserved process with numerous links to many human diseases, most notably cancer.
How does caspase-1 cause apoptosis?
Caspase-1 activated in inflammasomes triggers a programmed necrosis called pyroptosis, which is mediated by gasdermin D (GSDMD). Chemical dimerization of caspase-1 induces pyroptosis in GSDMD-sufficient cells, but apoptosis in GSDMD-deficient cells.
What is the function of caspase-1?
Caspase-1 is a cysteine protease that converts the inactive proform of IL-1β to the active inflammatory cytokine and hence represents an attractive target for the modulation of the effects of IL-1β (12,13).
What is caspase mediated apoptosis?
Caspases are a large family of evolutionarily conserved, aspartate-specific cysteine proteases that are essential for the initiation and execution of apoptosis1-3. Initiator caspases initiate the apoptosis signal while the executioner caspases carry out the mass proteolysis that leads to apoptosis.
What is it called when a cell dies?
If cells are no longer needed, they commit suicide by activating an intracellular death program. This process is therefore called programmed cell death, although it is more commonly called apoptosis (from a Greek word meaning “falling off,” as leaves from a tree).
Why is caspase so named?
They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β.
What activates NLRP3?
The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation.
Where is caspase-1 found?
Caspase-1 is evolutionarily conserved in many eukaryotes of the Kingdom Animalia. Due to its role in the inflammatory immune response, it is highly expressed in the immune organs such as the liver, kidney, spleen, and blood (neutrophils).
What does caspase do in apoptosis?
Caspases, a unique family of cysteine proteases, execute programmed cell death (apoptosis). Caspases exist as inactive zymogens in cells and undergo a cascade of catalytic activation at the onset of apoptosis. The activated caspases are subject to inhibition by the inhibitor-of-apoptosis (IAP) family of proteins.
How are caspases involved in cell death and inflammation?
Caspases in Cell Death, Inflammation, and Disease Caspases are an evolutionary conserved family of cysteine proteases that are centrally involved in cell death and inflammation responses. A wealth of foundational insight into the molecular mechanisms that control caspase activation has emerged in recent years.
What happens when over activation of caspase 3 occurs?
Conversely, over-activation of some caspases such as caspase -3 can lead to excessive programmed cell death. This is seen in several neurodegenerative diseases where neural cells are lost, such as Alzheimer’s disease. Caspases involved with processing inflammatory signals are also implicated in disease.
Where does caspase 8 form the death inducing signalling complex?
This FasR, FADD and pro-Caspase 8 form the Death Inducing Signalling Complex (DISC) where Caspase-8 is activated.
What is the role of caspase 14 in the epidermal barrier?
Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation. Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus.