Abstract
Oxidative stress is the main pathophysiological mechanism involved in the development of stroke. Severe DNA damage induced by oxidative stress or apoptotic stimuli activates poly (ADP-ribose) polymerase (PARP), causing a rapid depletion of nuclear NAD pools, cellular energy, and thiols. The biochemical activity of nicotinamide in the body is based on its conversion into NAD. Nicotinamide and its structural analogues possess a weak inhibitory effect on PARP. Nicotinamide exerts its neuroprotective effects by increasing NAD synthesis and ATP production indirectly and inhibiting PARP directly. By inhibiting PARP, membrane phosphatidylserine exposure and DNA fragmentation, nicotinamide can prevent brain necrosis and apoptosis effectively. Administration of nicotinamide at an early stage of stroke provides a new means to rescue the still viable but injured nerve cells within the ischemic and limit areas.
Keywords: Nicotinamide, DNA fragmentation, apoptosis, neuroprotective
Letters in Drug Design & Discovery
Title: Structure Activity Relationships for Nicotinamide in the Treatment of Stroke
Volume: 1 Issue: 1
Author(s): Jun Yang and James D. Adams Jr.
Affiliation:
Keywords: Nicotinamide, DNA fragmentation, apoptosis, neuroprotective
Abstract: Oxidative stress is the main pathophysiological mechanism involved in the development of stroke. Severe DNA damage induced by oxidative stress or apoptotic stimuli activates poly (ADP-ribose) polymerase (PARP), causing a rapid depletion of nuclear NAD pools, cellular energy, and thiols. The biochemical activity of nicotinamide in the body is based on its conversion into NAD. Nicotinamide and its structural analogues possess a weak inhibitory effect on PARP. Nicotinamide exerts its neuroprotective effects by increasing NAD synthesis and ATP production indirectly and inhibiting PARP directly. By inhibiting PARP, membrane phosphatidylserine exposure and DNA fragmentation, nicotinamide can prevent brain necrosis and apoptosis effectively. Administration of nicotinamide at an early stage of stroke provides a new means to rescue the still viable but injured nerve cells within the ischemic and limit areas.
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Cite this article as:
Yang Jun and Adams Jr. D. James, Structure Activity Relationships for Nicotinamide in the Treatment of Stroke, Letters in Drug Design & Discovery 2004; 1 (1) . https://dx.doi.org/10.2174/1570180043485716
DOI https://dx.doi.org/10.2174/1570180043485716 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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