title: Recent developments on the role of mitochondria in poly(ADP-ribose) polymerase inhibition.
abstract: Numerous pathophysiological disorders involve some element of oxidative stress and bioenergetic deficit. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been used recently as a promising new therapeutic strategy aimed at halting the bioenergetic decline associated with oxidative brain insults and other conditions. PARP-1 uses NAD+ as a substrate and is activated during stressful circumstances, mainly in the nucleus. PARP-1 inhibitors are well known for blocking the excessive consumption of NAD+, thereby preserving energy metabolism. But what is the role of mitochondria in this process? Recent investigations have begun to focus on whether mitochondrial function can also be preserved by PARP-1 inhibitors. This review will present some of the latest mechanistic evidence documenting the potential involvement of PARP-1 inhibitors in protecting mitochondrial function and preventing necrosis, apoptosis and mitochondrial calcium cycling.
authors.affiliation: University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Klaidman
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: M L
authors.initials: ML
authors.lastname: Chang
authors.forename: J D
authors.initials: JD
authors.lastname: Adams
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling; D002467:Cell Nucleus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009336:Necrosis; D018384:Oxidative Stress; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases