The role of caspases as executioners of apoptosis

Abstract

Caspases are a family of cysteine aspartyl proteases mostly involved in the execution of apoptotic cell death and in regulating inflammation. This article focuses primarily on the evolutionarily conserved function of caspases in apoptosis. We summarise which caspases are involved in apoptosis, how they are activated and regulated, and what substrates they target for cleavage to orchestrate programmed cell death by apoptosis.

Apoptotic cell death in disease—Current understanding of the NCCD 2023

“…MOMP is modulated by the activity of multiple pro-apoptotic and anti-apoptotic members of the BCL2, apoptosis regulator (BCL2) protein family [1056][1057][1058][1059][1060]. In response to apoptotic stimuli, MOMP leads to the sequential activation of the initiator caspase 9 (CASP9) and then executioner caspases CASP3 and CASP7 [12,13,[1061][1062][1063]. Two functionally distinct classes of pro-apoptotic BCL2 proteins have been identified.…”

“…From a biochemical perspective, an increasing number of RCD modalities have been defined by the Nomenclature Committee on Cell Death (NCCD) based on the mechanistic involvement of specific molecular components [ 1 , 11 ]. For instance, apoptotic cell death has been defined as a form of RCD that is promoted by proteases of the caspase family, namely caspase 3 (CASP3), CASP6 and CASP7, and initiated by CASP8 and CASP9 [ 1 , 12 , 13 ]. However, in mammalian organisms, with the exception of CASP8, apoptotic caspases simply accelerate RCD because their activation occurs when cells are already committed to die [ 1 , 14 – 16 ].…”

“…12 Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. 13 BIOGEM, Avellino, Italy. 14 Division of Systems Toxicology, Department of Biology, University of Konstanz, Konstanz, Germany.…”

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

“…Caspases are activated in both extrinsic (death receptor‐mediated) and intrinsic (mitochondria‐dependent) pathways during apoptosis process 23–25 (Figure 3). Caspases act as a set of intracellular cysteine proteases that cause genetically controlled cell death by destroying indispensable cellular proteins 26 . There are two forms of caspases involved in the process of apoptosis, namely initiating caspases (caspases 2, 8, 9, and 10) are activated by apoptosis‐related signaling pathways firstly, and then effector caspases (caspase 3, 6, and 7) are involved in the degradation of related proteins and organelles 27 .…”

Advances in the Therapeutic Effects of Apoptotic Bodies on Systemic Diseases

“…Caspase 9 is activated by the intrinsic pathway and caspase 8 and 10 are activated by the extrinsic pathway to mediate caspase 3 activation. Activated caspase 3 can initiate apoptosis by cleaving more than 1300 cell substrates [ 44 , 45 , 46 ]. Caspase 7 was considered to be redundant with caspase 3; however, caspase 7 activation requires caspase 1 inflammasomes under inflammatory conditions, while caspase 3 processing proceeds independently of caspase 1 [ 47 ].…”