Poly(ADP-ribose) Polymerase-1 in the Nervous System

Authors: Ha H.C.¹; Snyder S.H.²

Source: Neurobiology of Disease, Volume 7, Number 4, August 2000 , pp. 225-239(15)

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Abstract:

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. Copyright 2000 Academic Press.

Language: English

Document Type: Review article

Affiliations: 1: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205 2: Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205

Publication date: 2000-08-01