Caspase6

Caspase-6 is a cysteine protease belonging to the caspase family and is encoded by the CASP6 gene in humans. It is generally classified as an executioner caspase involved in the terminal stages of apoptosis, contributing to the dismantling of cellular components by cleaving a subset of substrates. In addition to its role in programmed cell death, Caspase-6 has been implicated in non-apoptotic cellular processes, including neuronal differentiation and certain forms of axonal degeneration.

Activation and mechanism of action are typical of caspases. Caspase-6 is synthesized as an inactive zymogen and becomes active following proteolytic processing by upstream initiator caspases within apoptotic signaling pathways. The mature enzyme forms from large and small subunits that assemble to create an active protease with a catalytic cysteine. Once activated, Caspase-6 cleaves substrates at specific aspartic acid sites, contributing to the orderly breakdown of cellular structures.

Substrates and functional consequences of Caspase-6 activity include cytoskeletal and nuclear components, and it has been shown to cleave lamin A/C among other targets. In neurons, Caspase-6 has been associated with neurodegenerative processes, including involvement in huntingtin cleavage in Huntington’s disease models and observed activity in affected brain regions of several disorders. These findings support a role for Caspase-6 in disease progression and tissue remodeling, beyond simple execution of cell death.

Clinical significance and research directions are focused on understanding Caspase-6's contribution to neurodegeneration and cancer. Elevated or dysregulated Caspase-6 activity has been detected in neurodegenerative disease contexts, making it a subject of interest as a potential biomarker and therapeutic target. Its precise roles can vary with cellular context and signaling environment.