Paraptosis

Paraptosis is a form of programmed cell death (PCD) that is morphologically and biochemically distinct from apoptosis and necrosis [1]. It is characterized by extensive cytoplasmic vacuolation, primarily resulting from the dilation of the endoplasmic reticulum (ER) and mitochondria [2]. Unlike apoptosis, paraptosis does not involve caspase activation, chromatin condensation, or the formation of apoptotic bodies [1, 2]. It is often triggered by the overactivation of certain receptors, such as the insulin-like growth factor 1 receptor (IGF-1R), or by stressors like proteasome inhibition and reactive oxygen species (ROS) accumulation [2, 4]. In the context of oncology, paraptosis has emerged as a promising therapeutic strategy for treating cancers that have developed resistance to conventional apoptosis-inducing therapies [2, 3]. Various natural and synthetic compounds, including curcumin and celastrol, have been shown to induce paraptosis in cancer cells, offering a way to bypass apoptotic blocks [2, 4]. However, the lack of a single definitive molecular marker and the potential for systemic toxicity remain challenges in its clinical application [1, 3].

Other names

Type III programmed cell deathCaspase-independent programmed cell deathNon-apoptotic programmed cell death

Induction of paraptosis through the promotion of endoplasmic reticulum (ER) stress, generation of reactive oxygen species (ROS), activation of MAPK/JNK signaling pathways, and inhibition of the proteasome.