Table 6.

BER in neurodegeneration

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