Caspasen

Acronym for "cysteine-aspartyl specific proteases" abbreviated caspases. Caspases are proteases (restriction endonucleases) that contain the amino acid cysteine in their active centre and cleave proteins behind the amino acid aspartate (cysteinyl aspartases).

The caspases are divided into:

• Initiator caspases (proCaspase- Caspase-2, Caspase-8, Caspase-9 and Caspase-10) - these are not involved in the actual apoptosis process,
• effector caspases (caspase-3, caspase-6 and caspase-7) - these are activated by the initiator caspases.

Furthermore, the inflammatory caspases caspase-1, caspase-4, caspase-5 and caspase-11 appear to trigger pyroptosis.

The activated caspase (see also inflammasome below) triggers a signaling cascade leading to apoptosis. Caspases are therefore closely linked to the process of apoptosis. To date, 14 different caspases have been identified in humans. They are arranged in signaling cascades. Extracellular signals initiate the activation of a membrane-bound cellular "death receptor", which triggers the first activations in the caspase cascade. Mitochondrial proteins such as cytochrome C are involved in the subsequent phase of caspase activation.

Caspase activation initially takes place in a complex with the"death receptor" and then in the apoptosome, whose components include cytochrome C, the protein Apaf-1, procaspase-9 and dATP. Procaspase-9 is proteolytically activated and released. It in turn activates procaspases 3, 6 and 7, which ultimately induce reactions via enzyme activation that inevitably lead to cell apoptosis. The apoptosis program can be interrupted by inhibiting caspases.

Some viruses, but also bacteria ( staphylococci), can prevent the death of the host cell by inhibiting caspases and thus ensure their own survival.

A special form of apoptosis is found in T lymphocytes (see cytotoxic T cell below). A T cell is activated via its receptor, the TZR(T cell receptor).

A renewed activation of an already activated T cell leads to the formation of reactive oxygen species (ROS) and the release of intracellular calcium. These two signals lead to the formation of CD95L, the ligand of CD95 (CD95 = APO-1= FAS), which is released from the cell. Here it can bind to the CD95 receptor (CD95R) of its own cell or neighboring cells, which leads to apoptosis. This type of apoptosis is known as activation-induced cell death (AICD) and plays a role in the termination of immune responses.