Structure and Activation

• Caspase 3 (CASP3) is a crucial member of the cysteine-aspartic acid protease (caspase) family.
• Synthesized as an inactive 32 kDa proenzyme, activated through proteolytic processing into two large (17 kDa) and two small (12 kDa) subunits.
• Activation occurs via extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic pathways.
• Upstream initiator caspases (caspase 8, 9, or 10) cleave procaspase 3 at specific aspartate residues.
• Active site contains a conserved QACXG pentapeptide motif essential for catalytic activity.

Role in Apoptotic Cell Death

• Caspase 3 coordinates the breakdown of cellular elements by cleaving structural and operational proteins.
• Key proteins targeted include poly (ADP-ribose) polymerase (PARP), inhibitor of caspase-activated DNase (ICAD), gelsolin, and others.
• Activation leads to DNA fragmentation, membrane changes, and formation of apoptotic bodies.
• Regulated by Inhibitor of Apoptosis Protein (IAP) family to prevent unintended cell death.

Developmental Functions and Tissue Homeostasis

• Essential for tissue and organ development, especially in brain growth and differentiation of precursor cells.
• Necessary for the elimination of developing lymphocytes that don't meet standards, maintaining tolerance.
• Plays roles in muscle differentiation, lens formation, and digit separation during limb growth.
• In adult tissues, maintains tissue balance by removing damaged, infected, or excess cells.

Pathological Implications

• Caspase 3 dysfunction linked to various health issues:
• Insufficient activity promotes cancer growth by allowing damaged cells to survive and multiply.
• Overactivity contributes to diseases like: Alzheimer's, Parkinson's, and heart conditions.
• Autoimmune problems may arise from caspase 3-mediated cell death in self-reactive cells.

Therapeutic Applications and Clinical Significance

• Targeting caspase 3 for treatments and therapies:
• Activating caspase 3 in tumor cells for cancer treatment using chemicals or gene therapy.
• Inhibiting caspase 3 for managing diseases like neurodegenerative conditions and minimizing tissue damage post-stroke or heart attacks.
• Diagnostic tool for identifying cell death in clinical samples and assessing treatment effectiveness.
• Innovative imaging methods utilizing CASP3 agents for non-invasive apoptosis tracking in disease states.