Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD) brain

Lovell, Mark A.; Soman, Sony; Bradley, Melissa A.

doi:10.1016/j.mad.2011.08.003

Cited by 112 publications

(80 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In light of these data and the results of other research teams, it can be stated that the processes associated with DNA damage are important in the formation and development of neurodegenerative diseases including AD [24,25]. Moreover, endo- and exogenous DNA damage can be a significant marker for the degenerative changes that occur in neurons and glial cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk

Kwiatkowski

Czarny²,

Toma³

et al. 2016

Neuropsychobiology

View full text Add to dashboard Cite

Background: One of the factors that contribute to Alzheimer's disease (AD) is the DNA damage caused by oxidative stress and inflammation that occurs in nerve cells. It has been suggested that the risk of AD may be associated with an age-dependent reduction of the DNA repair efficiency. Base excision repair (BER) is, among other things, a main repair system of oxidative DNA damage. One of the reasons for the reduced efficiency of this system may be single-nucleotide polymorphisms (SNP) of the genes encoding its proteins. Methods: DNA for genotyping was obtained from the peripheral blood of 281 patients and 150 controls. In the present study, we evaluated the impact of 8 polymorphisms of 6 BER genes on the AD risk. We analyzed the following SNP: c.-468T>G and c.444T>G of APEX1, c.*50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1. Results: We showed that the LIG1 c.-7C>T A/A and LIG3 c.*83A>C A/C variants increased, while the APEX1 c.444T>G G/T, LIG1 c.-7C>T G/, LIG3 c.*83A>C C/C variants reduced, the AD risk. We also evaluated the relation between gene-gene interactions and the AD risk. We showed that combinations of certain BER gene variants such as c.977C>G×c.*50C>T CC/CT, c.444T>G×c.*50C>T GG/CT, c.-468T>G×c.*50C>T GG/CT, c.-441G>Ac.*50C>T×c.*50C>T GG/CT, c.*83A>C× c.*50C>T CT/AC, and c.-7C>T×c.*50C>T CT/GG can substantially positively modulate the risk of AD. Conclusions: In conclusion, we revealed that polymorphisms of BER genes may have a significant effect on the AD risk, and the presence of polymorphic variants may be an important marker for AD.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In the case of LIG3 an association between c.*50C>T and young-onset lung cancer was shown. Carriers of minor homozygotes exhibited an increased risk for this disease (OR 2.05) [55]. …”

Section: Discussionmentioning

confidence: 99%

Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk

Kwiatkowski

Czarny²,

Toma³

et al. 2016

Neuropsychobiology

View full text Add to dashboard Cite

show abstract

“…In our analysis, BER genes ( OGG1 , TDG , and UNG) show altered levels of 5-hmC in the hippocampus and show decreased expression throughout the progression of AD (Weissman et al . 2007, Lovell et al . 2011).…”

Section: Discussionmentioning

confidence: 99%

Single-Base Resolution Mapping of 5-Hydroxymethylcytosine Modifications in Hippocampus of Alzheimer’s Disease Subjects

2017

Self Cite

View full text Add to dashboard Cite

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our data show significant pathways for altered levels of 5- hmC in the hippocampus of AD subjects compared to age-matched normal controls involved in signaling, energy metabolism, cell function, gene expression, protein degradation, and cell structure and stabilization. Overall, our data suggest a possible role for the dysregulation of epigenetic modifications to cytosine in late stage AD.

show abstract

“…Increased amounts of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde which are products of lipid peroxidation [18] have been found on post-mortem analysis of human brains from aceruloplasminemia patients [19]. Protein carbonyl groups and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxdG) as markers of oxidative damage to proteins and DNA can be detected in tissue of various neurodegenerative disorders including AD [20][21][22][23]. Also, depletion of endogenous antioxidants such as glutathione has been documented in the substantia nigra of PD patients further supporting the role of oxidative stress in neurodegeneration [24].…”

Section: Causes and Consequences Of Cerebral Iron Accumulationmentioning

confidence: 99%

Iron chelation in the treatment of neurodegenerative diseases

Dušek

Schneider

Aaseth

2016

Journal of Trace Elements in Medicine and Biology

106

View full text Add to dashboard Cite

a b s t r a c tDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

show abstract

Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD) brain

Cited by 112 publications

References 38 publications

Association between Single-Nucleotide Polymorphisms of the <b><i>hOGG1,</i></b><b><i>NEIL1,</i></b><b><i>APEX1, FEN1,</i></b><b><i>LIG1,</i></b> and <b><i>LIG3</i></b> Genes and Alzheimer's Disease Risk

Association between Single-Nucleotide Polymorphisms of the <b><i>hOGG1,</i></b><b><i>NEIL1,</i></b><b><i>APEX1, FEN1,</i></b><b><i>LIG1,</i></b> and <b><i>LIG3</i></b> Genes and Alzheimer's Disease Risk

Single-Base Resolution Mapping of 5-Hydroxymethylcytosine Modifications in Hippocampus of Alzheimer’s Disease Subjects

Iron chelation in the treatment of neurodegenerative diseases

Contact Info

Product

Resources

About