Table 6.
Disease | Study | Results | Selected References |
---|---|---|---|
Alzheimer’s Disease- age related dementia | AD patients and age-matched controls | Increased 8-oxoG in ventricular CSF DNA; decreased free 8-oxoG indicating accumulation of 8-oxoG lesions in patients. | Lovell et al., 1999 |
Late stage AD patients and early stage with mild cognitive impairment | Elevated 8-oxoG, 8-OHA, and 5,6-diamino-5-formamidopyrimidine in nuclear and mtDNA isolated from vulnerable brain regions in amnestic mild cognitive impairment. | Lovell and Markesbery, 2007 | |
Brain tissue autopsies | Immunoreactivity to hOGG1-2a is associated with neurofibrillary tangles, dystrophic neurites and reactive astrocytes in AD. | Iida et al., 2002 | |
Post-mortem autopsies graded for disease progression. | POL-β is increased with increasing severity of disease; decreases with severe neuronal loss. Suggests POL-β involved early in AD pathology. | Copani et al., 2006 | |
Postmortem AD midfrontal cortex and age-matched controls. | APE1 expression significantly increased in AD subjects. | Davydov et al., 2003 | |
Post-mortem autopsies sporadic AD, mild cognitive impaired and age-matched controls. | Significant BER deficiencies; decreased OGG-BER, UDG-BER and POLβ activities. No decrease in APE1-BER. Decreases seen in both AD and mild cognitive impairment. | Weissman et al., 2007b | |
Parkinson’s Disease | Autopsies PD and age-matched controls. | Up-regulation of MYH in the mitochondria of substantia nigra. | Arai et al., 2006 |
Amyotrophic Lateral Sclerosis | Mutant SOD mice | POLβ and mitochondrial OGG1 is decreased in symptomatic mice. POLγ is decreased in presymptomatic and symptomatic mice. | Murakami et al., 2007 |
Patients with familial ALS | Identified missense mutations in the APE1 gene. | Olkowski, 1998 | |
Patients with sporadic ALS and age-matched controls. | APE1 levels and activity are significantly lower in ALS subjects than in controls. | Kisby et al., 1997 | |
Patients with sporadic ALS and age-matched controls. | Results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sporadic ALS pathogenesis. | Coppede et al., 2007 | |
Ischemia | Mouse and rat models | Ischemia causes transient decrease in BER proteins in the brain. Ischemic preconditioning increases BER capacity. | Chen et al., 2003a; Fujimura et al., 1999; Lan et al., 2003; Li et al., 2007b; Li et al., 2006; Luo et al., 2007 |
UNG −/− mice | Increased post-ischemic brain injury compared to wild type mice. | Endres et al., 2004 | |
PARP1 −/− mice | PARP1 critical in ischemia-reperfusion injury. | Shall and de Murcia, 2000 | |
PARP2 −/− mice | Reduced stroke damage in PARP2 −/− mice. | Kofler et al., 2006 | |
Huntington’s Disease-trinucleotide instability | HD gene transgenic mice bred with MPG, OGG1 and NTH1 knockouts. | OGG1 excision of 8-oxo-G within CAG repeat DNA can initiate strand displacement and expansion in vitro during BER, creating a toxic oxidation cycle. | Kovtun et al., 2007 |
AD = Alzheimer’s disease; 8-oxoG = 8-oxodeoxyguanine; 8-OHA=8-hydroxyadenine; mtDNA=mitochondrial DNA; hOgg1-2a=mitochondrial splice variant of hOgg1; OGG/UDG/APE-BER=complete base excision repair assay of OGG/UDG/APE substrate; PD=Parkinson’s disease; SOD=superoxide dismutase; ALS= Amyotrophic Lateral Sclerosis; HD=Huntington’s disease