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Poly (ADP-ribose) polymerase, nitric oxide and cell death
1Department of Neuroscience, The Johns Hopkins University, School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Trends in Pharmacological Sciences
|May 14, 1999
Summary
Poly (ADP-ribose) polymerase (PARP) activation by DNA breaks can cause cell death. PARP inhibitors show promise for treating various clinical disorders by protecting tissues from damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme crucial for DNA repair.
- Excessive PARP activation, triggered by DNA strand breaks, depletes nicotinamide adenine dinucleotide (NAD) and ATP, leading to cell death.
- Conditions like CNS damage, stroke, and myocardial infarction involve DNA damage and PARP activation.
Purpose of the Study:
- To investigate the role of PARP in DNA repair and cell death.
- To evaluate the therapeutic potential of PARP inhibitors and gene deletion in various disease models.
Main Methods:
- Studies on PARP activation in response to DNA strand breaks.
- Assessment of PARP inhibitors and gene deletion in models of CNS damage, myocardial infarction, and diabetes.
Main Results:
- Excessive PARP activation leads to NAD and ATP depletion, causing cell death.
- PARP inhibition or gene deletion demonstrated significant protective effects against tissue damage in models of stroke, myocardial infarction, and toxin-induced diabetes.
Conclusions:
- PARP plays a critical role in cellular responses to DNA damage.
- PARP inhibitors represent a promising therapeutic strategy for a broad spectrum of clinical disorders involving tissue damage.