Parthanatos cell death pathway

Parthanatos is a distinct form of regulated, caspase-independent cell death characterized by the overactivation of poly(ADP-ribose) polymerase 1 (PARP-1) [1.1.1, 1.3.4]. This overactivation leads to the accumulation of poly(ADP-ribose) (PAR) polymers, which act as death signals that trigger the release of apoptosis-inducing factor (AIF) from the mitochondria into the cytoplasm [1.3.3, 1.3.4]. AIF then translocates to the nucleus, where it associates with macrophage migration inhibitory factor (MIF) to form a complex that causes large-scale DNA fragmentation and irreversible cell death [1.1.1, 1.3.2]. This pathway is a major driver of neuronal loss in neurodegenerative diseases like Parkinson's and Alzheimer's, as well as tissue damage in stroke and myocardial infarction [1.1.1, 1.3.2]. Conversely, in oncology, inducing parthanatos is explored as a strategy to eliminate cancer cells that have developed resistance to traditional apoptosis [1.3.1, 1.3.3]. Therapeutic strategies focus on inhibiting PARP-1, blocking AIF translocation, or specifically targeting the nuclease activity of MIF [1.1.1, 1.3.5]. While PARP inhibitors are clinically validated in cancer, their application in neuroprotection requires careful management to avoid compromising physiological DNA repair processes [1.3.2, 1.3.5].

Other names

PARP-1-dependent cell deathPAR-dependent cell deathPAR-mediated cell death

Inhibition of Poly(ADP-ribose) polymerase 1 (PARP-1) to prevent PAR accumulation; Inhibition of Macrophage migration inhibitory factor (MIF) nuclease activity to block DNA fragmentation; Inhibition of Apoptosis-inducing factor (AIF) nuclear translocation; Degradation of Poly(ADP-ribose) (PAR) polymers.