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Recent Developments on the Role of Mitochondria in Poly(ADP-ribose) Polymerase Inhibition

[ Vol. 10 , Issue. 24 ]

Author(s):

L. K. Klaidman, J. Yang, M. L. Chang and J. D. Adams Jr.   Pages 2669 - 2678 ( 10 )

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.

Keywords:

nicotinamide, poly(adp-ribose) polymerase, mitochondria

Affiliation:

USC School of Pharmacy, 1985 Zonal Avenue, PSC 508, Los Angeles, CA 90089, USA.



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