Nervous system functions of poly(ADP-Ribose) polymerase-1

Krishna Juluri, Hyo Chol Ha, Solomon H. Snyder

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) was first identified as a nuclear enzyme involved in DNA repair,1,2 and as such was of principal interest to studies of the cell cycle and alterations that can lead to cancer. PARP-1 catalyzes the initiation, elongation, and branching of ADP-ribose polymers, derived from the substrate nicotinamide adenine dinucleotide (NAD+) on to glutamate and aspartate residues of acceptor proteins.3 Evidence that PARP-1 overactivation following cell stress can kill cells by energy depletion4 led to the notion that PARP inhibition might be cytoprotective. Because neurons in the central nervous system generally do not divide in adult life, and because energy dynamics in the nervous system tend to be relatively sequestered from events in the rest of the body, studies of PARP-1 in the nervous system have been relatively recent. However, abundant evidence now indicates that PARP-1 overactivation plays a major role in neurotoxicity of various conditions including stroke, and that PARP inhibition may provide a more powerful means of preventing stroke damage than many other pharmacological approaches.5 Studies involving neural as well as other tissues indicate that cell death by PARP-1 overactivation may be selectively associated with necrotic cell death, thus providing a “programmed” necrosis in parallel to the programmed cell death (apoptosis) that has been extensively characterized. PARP-1 also appears to play a unique role in facilitating viral integration into the host genome. Finally, studies in the nervous system and other tissues establish a role for PARP-1 in normal, physiological processes unrelated to pathophysiological cell death and linked in part to nitric oxide (NO) biology.

Original languageEnglish (US)
Title of host publicationPARP as a Therapeutic Target
PublisherCRC Press
Pages1-18
Number of pages18
ISBN (Electronic)9781420042405
ISBN (Print)0849300738, 9780849300738
StatePublished - Jan 1 2002

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ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Juluri, K., Ha, H. C., & Snyder, S. H. (2002). Nervous system functions of poly(ADP-Ribose) polymerase-1. In PARP as a Therapeutic Target (pp. 1-18). CRC Press.