Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. In mammalian cells, cell death often continues when caspases are inhibited or deleted. Caspase-independent PCD, mediated by other proteases or signaling components, has been described in numerous publications. Accumulating evidence has suggested that non-caspases, including cathepsins, calpains, granzymes, and the proteasome complex, also have roles in mediating and promoting cell death. Caspase-independent cell death pathways are important safeguard mechanisms to protect the organism against unwanted and potentially harmful cells when caspase-mediated routes fail but can also be triggered in response to cytotoxic agents or other death stimuli.

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