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Increased oxidative damage to DNA in ALS patients.
M Bogdanov1, R H Brown, W Matson
1Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Free Radical Biology & Medicine
|October 18, 2000
Summary
Oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8OH2'dG) was elevated in ALS patients. Its increase over time correlated with disease severity, suggesting a role for oxidative stress in ALS progression.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with unknown etiology.
- Oxidative toxicity is strongly implicated in neuronal death in ALS.
- 8-hydroxy-2'-deoxyguanosine (8OH2'dG) is a validated biomarker of oxidative DNA damage.
Purpose of the Study:
- To investigate 8OH2'dG levels in biological fluids of ALS patients.
- To assess the longitudinal changes in 8OH2'dG and their correlation with disease progression and severity.
Main Methods:
- Measured 8OH2'dG levels in plasma, urine, and cerebrospinal fluid (CSF) from ALS patients and controls.
- Monitored changes in 8OH2'dG levels over 9 months in ALS patients and controls.
- Correlated 8OH2'dG levels and rates of change with ALS disease severity.
Main Results:
- Significantly elevated 8OH2'dG levels were observed in plasma, urine, and CSF of ALS patients compared to controls.
- Plasma and CSF 8OH2'dG levels increased with age in all subjects.
- 8OH2'dG levels in plasma and urine increased significantly over time exclusively in the ALS group.
- The rate of increase in urinary 8OH2'dG correlated significantly with ALS disease severity.
Conclusions:
- Findings support the hypothesis that oxidative pathology is integral to the neurodegenerative process in ALS.
- Elevated and increasing 8OH2'dG levels may serve as a valuable biomarker for monitoring ALS progression.
- 8OH2'dG could be a useful tool for evaluating therapeutic interventions in amyotrophic lateral sclerosis.