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

Kwiatkowski, Dominik; Czarny, Piotr; Toma, Monika; Korycinska, Anna; Sowinska, Katarzyna; Gałecki, Piotr; Bachurska, Agnieszka; Bielecka-Kowalska, Anna; Szemraj, Janusz; Maes, Michaël; Śliwiński, Tomasz

doi:10.1159/000444643

Cited by 21 publications

(9 citation statements)

References 60 publications

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“…Creb1 and its binding partners play a well-documented critical role in nervous system development and in the protective response to neuron stressors 62 . Creb1 dysregulation is likely to be involved in Alzheimer’s disease 65 , Parkinson’s disease, Huntington’s disease, Rubinstein-Taybi syndrome, ischemia, alcoholism, schizophrenia, addiction, and depression (reviewed in Sakamoto et al 62 and Thakur et al 66 ). In the mature CNS, Creb1 mediates transcription of multiple factors required for neuronal survival.…”

Section: Discussionmentioning

confidence: 99%

AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair

et al. 2019

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Brain and neurons are particularly sensitive to reactive oxygen species (ROS). Oxidative damage from ROS results in increased 8-oxoguanine in DNA followed by repair through the base excision repair (BER) pathway. We reported earlier that AP endonuclease 1 (Apex1) not only participates directly in BER but also regulates transcription factor Creb1. Here, we investigated how Apex1 affects brain to respond effectively to oxidative damage during zebrafish development. Loss of Apex1 resulted in increased ROS, 8-oxoguanine, and abasic sites as well as loss of Ogg1, which recognizes 8-oxoguanine and is required for its repair. Moreover, knock-down of Apex1 not only resulted in reduction of expression of several major proteins in the BER pathway (Polb and Ogg1), and it also resulted in maldistribution and loss of four key brain transcription factors ( fezf2 , otx2 , egr2a , and pax2a ), leading to abnormal brain development. These results were independent of p53 protein level. In contrast, exposure to exogenous H 2 O 2 resulted in increased transcription and protein of Apex1 along with other BER components, as well as Creb1. Taken together, these results indicate that oxidative stress increased when the level of Apex1 was reduced, revealing a novel pathway of how Apex1 manages oxidative stress in developing brain.

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Section: Discussionmentioning

confidence: 99%

AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair

et al. 2019

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“…A recent study demonstrated that downregulation of NEIL1 expression in the lymphocytes of LOAD patients is not due to the methylation status of NEIL1 promoter [33]. In another study, Kwiatkowski et al conducted SNP genotyping assay on peripheral blood samples from LOAD patients and controls, and suggested that the combination of NEIL1 rs4462560 (p = 0.511) and 8-oxoguanine DNA glycosylase gene ( OGG1 ) rs1052133 (p = 0.535) increases the risk of LOAD (OR = 2.24, 95% CI = 1.36–3.91, p = 0.041) [36]. In the present study, the NGS primers do not cover NEIL1 rs4462560 location (Table 1, S1 Fig and S1 Table).…”

Section: Discussionmentioning

confidence: 99%

“…However, not all BER genes have been screened for their association with reduced BER capacity in LOAD patients and with LOAD development using targeted next generation sequencing (NGS) technology. Several studies have demonstrated no association between predominant variant of 8-oxoguanine DNA glycosylase ( OGG1 ) gene, Ser326Cys, and LOAD risk [36,37,39,43]. Another mutations of OGG1 , A53T, A288V and C796del, that cause a decrease in OGG1 activity have been identified in brain tissues of LOAD patients, but not in control tissues [41,42].…”

Section: Introductionmentioning

confidence: 99%

“…Since one patient has OGG1 A53T, one patient has A288V and two patients have C796del out of 14 LOAD patients, large cohort studies are required for the association of these variants with LOAD risk [42]. No statistically significant association between the LOAD risk and several different BER gene variants has been identified, including OGG1 Arg46Gln [37], MUTYH c.972G/C [35], NEIL1 c.-283C/G [36], APE1 (c.-468T/G and c.444T/G) [36,43], FEN1 c.-441C/A [36], LIG3 c.-50C/T [36] and XRCC1 Arg280His, Arg399Gln and Arg194Trp [40,43,44]. However, Kwiatkowski et al screened 110 patients and 120 healthy controls and found that G/A genotype of XRCC1 rs25487 (Arg399Gln) increases the LOAD risk, but A/A genotype decreases the risk [35].…”

Section: Introductionmentioning

confidence: 99%

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Investigation of base excision repair gene variants in late-onset Alzheimer’s disease

Ertuzun¹,

Semerci

Çakır

et al. 2019

PLoS ONE

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Base excision repair (BER) defects and concomitant oxidative DNA damage accumulation play a role in the etiology and progression of late-onset Alzheimer’s disease (LOAD). However, it is not known whether genetic variant(s) of specific BER genes contribute to reduced BER activity in LOAD patients and whether they are associated with risk, development and/or progression of LOAD. Therefore, we performed targeted next generation sequencing for three BER genes, uracil glycosylase ( UNG ), endonuclease VIII-like DNA glycosylase 1 ( NEIL1 ) and polymerase β ( POLβ ) including promoter, exonic and intronic regions in peripheral blood samples and postmortem brain tissues (temporal cortex, TC and cerebellum, CE) from LOAD patients, high-pathology control and cognitively normal age-matched controls. In addition, the known LOAD risk factor, APOE was included in this study to test whether any BER gene variants associate with APOE variants, particularly APOE ε4. We show that UNG carry five significant variants (rs1610925, rs2268406, rs80001089, rs1018782 and rs1018783) in blood samples of Turkish LOAD patients compared to age-matched controls and one of them ( UNG rs80001089) is also significant in TC from Brazilian LOAD patients (p<0.05). The significant variants present only in CE and TC from LOAD are UNG rs2569987 and POLβ rs1012381950, respectively. There is also significant epistatic relationship (p = 0.0410) between UNG rs80001089 and NEIL1 rs7182283 in TC from LOAD subjects. Our results suggest that significant BER gene variants may be associated with the risk of LOAD in non- APOE ε4 carriers. On the other hand, there are no significant UNG , NEIL1 and POLβ variants that could affect their protein level and function, suggesting that there may be other factors such as post-transcriptional or–translational modifications responsible for the reduced activities and protein levels of these genes in LOAD pathogenesis. Further studies with increased sample size are needed to confirm the relationship between BER variants and LOAD risk.

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“…DNA repair and antioxidant enzymes (defense systems) protect against the development of diseases. There are many published studies on antioxidant enzyme activity, DNA repair enzymes and OS‐related diseases . These defense systems have important roles in the development of IS.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress gene polymorphisms may have an impact in the development of ischemic stroke

Karahalıl

Orhan

2017

The Journal of Gene Medicine

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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

Cited by 21 publications

References 60 publications

AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair

AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair

Investigation of base excision repair gene variants in late-onset Alzheimer’s disease

Oxidative stress gene polymorphisms may have an impact in the development of ischemic stroke

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