Poly(ADP-ribose) polymerase-1 in the nervous system

Neurobiol Dis. 2000 Aug;7(4):225-39. doi: 10.1006/nbdi.2000.0324.


Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme, activated by DNA strand breaks to participate in DNA repair. Overactivation of PARP by cellular insults depletes its substrate NAD(+) and then ATP, leading to a major energy deficit and cell death. This mechanism appears to be prominent in vascular stroke and other neurodegenerative processes in which PARP gene deletion and PARP-inhibiting drugs provide major protection. Cell death associated with PARP-1 overactivation appears to be predominantly necrotic while apoptosis is associated with PARP-1 cleavage, which may conserve energy needed for the apoptotic process. Novel forms of PARP derived from distinct genes and lacking classic DNA-binding domains may have nonnuclear functions, perhaps linked to cellular energy dynamics.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Apoptosis / physiology*
  • Cell Death / physiology
  • Humans
  • NAD / metabolism*
  • Necrosis
  • Nervous System Physiological Phenomena
  • Neurons / physiology*
  • Poly(ADP-ribose) Polymerases / physiology*


  • NAD
  • Adenosine Triphosphate
  • Poly(ADP-ribose) Polymerases