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Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in multiple neurologic
diseases by mediating caspase-independent cell death, which has recently been designated
parthanatos to distinguish it from other forms of cell death such as apoptosis, necrosis
and autophagy. Mitochondrial apoptosis-inducing factor (AIF) release and translocation
to the nucleus is the commitment point for parthanatos. This process involves a pathogenic
role of poly(ADP-ribose) (PAR) polymer. It generates in the nucleus and translocates
to the mitochondria to mediate AIF release following lethal PARP-1 activation. PAR
polymer itself is toxic to cells. Thus, PAR polymer signaling to mitochondrial AIF
is the key event initiating the deadly crosstalk between the nucleus and the mitochondria
in parthanatos. Targeting PAR-mediated AIF release could be a potential approach for
the therapy of neurologic disorders.