kaspase3

Kaspase-3, also known as CPP32, is a cysteine aspartate-specific protease that plays a crucial role in programmed cell death, specifically apoptosis. It is a member of the caspase family, which are involved in various forms of cell death, including apoptosis, necrosis, and pyroptosis. Kaspase-3 is activated by upstream caspases, such as kaspase-8 and kaspase-9, and it subsequently cleaves and activates downstream effector caspases, leading to the execution of apoptosis.

The activation of kaspase-3 is a key event in the intrinsic and extrinsic pathways of apoptosis. In the intrinsic pathway, kaspase-3 is activated by the mitochondrial pathway, where it is released from the mitochondria in response to various stimuli, such as DNA damage or oxidative stress. In the extrinsic pathway, kaspase-3 is activated by death receptors, such as Fas and TNF-alpha, which recruit and activate kaspase-8, which in turn activates kaspase-3.

Kaspase-3 is a homodimeric protein, and its activation involves the formation of a heterotetrameric complex with kaspase-6 or kaspase-7. This complex then cleaves and activates downstream effector caspases, such as kaspase-2 and kaspase-9, leading to the execution of apoptosis. The cleavage of specific substrates by kaspase-3, such as poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF45), is a hallmark of apoptosis.

Kaspase-3 inhibitors have been developed as potential therapeutic agents for various diseases, including cancer and neurodegenerative disorders. However, the use of kaspase-3 inhibitors is controversial, as they may also inhibit the beneficial effects of apoptosis, such as the clearance of infected cells and the prevention of autoimmune responses. Therefore, the development of more specific and selective caspase inhibitors is an active area of research.