Caspase family protease (Caspase)

Caspase family proteases are a group of cysteine-dependent aspartate-specific proteolytic enzymes essential for controlling programmed cell death (apoptosis) and coordinating inflammation[1][2][3][4][6]. Caspases are expressed as inactive precursors (procaspases) that are activated by specific signals through proteolysis, allowing them to cleave substrates after aspartic acid residues[1][2][7]. They are divided into initiator caspases, which begin apoptotic signaling cascades, and effector caspases, which execute apoptosis by cleaving various cellular targets[2][9]. Besides their central roles in apoptosis, many caspases contribute to inflammatory responses (such as caspase-1 processing pro-IL1β), different modes of programmed cell death (pyroptosis, necroptosis, PANoptosis), cell proliferation, differentiation, neural development, and cancer suppression[1][3][4][8]. Dysregulation of caspase activity is implicated in the development and progression of cancers, autoimmune diseases, neurodegenerative conditions, and inflammatory disorders[2][3][8]. Several inhibitors have reached clinical trials for conditions involving excessive or pathogenic programmed cell death or inflammation. However, therapeutic targeting of caspases carries risks of impaired physiological cell turnover, immune response, and tissue repair[2][3][6]. Caspases belong to the peptidase family C14 within clan CD and are structurally and mechanistically distinct from related peptidase families such as metacaspases and paracaspases[5][7]. In humans, 12 caspases are recognized, each classified by substrate specificity and sequence features[3][7][9]. Caspases are highly conserved, playing essential and regulated roles across evolutionarily diverse organisms[1][3][5].

Other names

cysteine aspartic proteasecysteine aspartasecysteine-dependent aspartate-directed proteaseICE (for Caspase-1, historical)interleukin-1β-converting enzyme (for Caspase-1)CPP32/apopain/Yama (for Caspase-3, historical)

Inhibition of caspase enzymatic activity (prevents cleavage of apoptotic or inflammatory substrates), apoptotic pathway modulation, anti-inflammatory action via inhibition of cytokine processing