PMID: 9437658Jan 23, 1998Paper

The effects of aging and neurodegeneration on apoptosis-associated DNA fragmentation and the benefits of nicotinamide

Molecular and Chemical Neuropathology
Suman K Mukherjee, J D Adams

Abstract

In this work, the tertiary butylhydroperoxide- (t-BuOOH) treated mouse was used as a model to study the oxidative stress that is associated with various neurodegenerative diseases. DNA was found to be an early target of t-BuOOH attack. Necrosis was associated with extensive DNA fragmentation that occurred in almost all regions of the brain within 20 min following intracerebroventricular (icv) injection of 109.7 mg/kg t-BuOOH. Apoptosis was associated with high levels of DNA fragmentation that was observed at 48 h after icv administration of 21.9 mg/kg t-BuOOH. Susceptibility to DNA damage was found to be age-dependent, since 24-mo-old mice exhibited consistently higher and more pervasive DNA damage than 8 mo-old-mice. Extensive DNA damage was seen in various brain regions in patients with Alzheimer disease (AD) and with both Alzheimer and Parkinson disease (AD-PD). These results directly implicate DNA damage in neurodegeneration. The DNA fragmentation ob-served can lead to both apoptosis and necrosis, as suggested by gel electrophoresis. Nicotinamide, a precursor of NAD in the brain, was able to prevent DNA fragmentation induced by low-dose t-BuOOH, when coadministered with the toxin.

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Citations

Feb 5, 2000·Redox Report : Communications in Free Radical Research·J P Kamat, T P Devasagayam
Mar 16, 2007·Phytotherapy Research : PTR·Yashodharan KumarasamySatyajit D Sarker
Jan 1, 2006·Toxicology Mechanisms and Methods·Suraj G BhansaliSuman K Mukherjee
Jun 1, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paul D ChastainDavid G Kaufman
May 9, 2001·Biochimica Et Biophysica Acta·L K KlaidmanJ D Adams

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis