Track topics on Twitter Track topics that are important to you
Caspases are a family of enzymes with very specific characteristics that can be used in almost every biological pathway in the body. The knock-on effects of the action of caspases keep us alive, initiating many vital cellular pathways. Interestingly, caspases are the activated form of a pre-cursor molecule called zymogens, which can be activated by a number of different factors. Some caspases are activated by fas in the pro-apoptosis cell pathway, and then go on to activate further caspases (caspase 3), which induce apoptosis, while others interact with Apaf-1 in other cell pathways. On thing in common with all the molecules that caspases interact with are the CARD (caspase recruitment domain) domains that are the site of the interaction. Typically, these consist of 100 amino acids that are the correct order such that they bind with the target site of caspases and can induce structural changes that render the caspase active.
In the same way caspases are activated, many anti-apoptotic molecules can also inhibit caspases to prevent cell death, by a similar mechanism of structural alteration.
There are 14 main caspases which have a variety of functions from cleaving to activation through other mechanisms to produce active molecules.
The relative activity of caspase molecules has been implicated in a number of diseases from a specific form of encephalitis (reovirus-induced), psoriasis and several cancers. This is important in that it provides researchers with therapeutic targets for drug development. For example, in drug-resistant forms of cancer, caspase-8 is in part responsible for making cells responsive to combination therapies such as eroltinib and cell-cycle inhibitiors. Caspase 6 is implicated in the degeneration of axons in Alzheimer’s disease. Research has suggested that activation of caspase 6 is controlled by pro-Caspase-6a, which is in turn controlled by pro-Caspase-6b, and thus either could be a therapeutic target for drugs to prevent axonal degeneration in patients with Alzheimers. Further neurological implications include the caspase-3 dependent cell death in cerebellar granule neurons, which highlights potential neuro-toxicity of any caspase inhibiting compound.
The value of the caspase market is hard to establish, since while central to many mechanisms of actions for many drugs, these drugs act slightly further upstream, modulating the relative activity of caspase molecules, but it is clear that they offer significant potential for R&D in pharma!