Prostate apoptosis response protein (PAR4) is a proapoptotic protein with intracellular functions in the cytoplasm and nucleus, capable of suppressing tumors (1). Extracellular PAR4 induces apoptosis by binding to the stress response protein, glucose-regulated protein-78 (GRP78), via an extrinsic pathway (1). PAR4 contains leucine zipper and death domains that are upregulated in prostate cancer cells and hippocampal neurons induced to undergo apoptosis (2). Alzheimer’s and Parkinson’s diseases are both targets for PAR-4 in treatments that block its expression, preventing neuronal cell death (3). In Parkinson’s disease, the death of dopaminergic neurons follows a degenerative pathway that circumvents the apoptotic induction of PAR-4 (4). An isoform of PAR-4, PAR-4/p33, prevents apoptosis in neural stem cells and does not activate caspase 3 (5).
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