Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer

Thanan, Raynoo; Oikawa, Shinji; Hiraku, Yusuke; Ohnishi, Shiho; Ma, Ning; Pinlaor, Somchai; Yongvanit, Puangrat; Kawanishi, Shosuke; Murata, Mariko

doi:10.3390/ijms16010193

Cited by 363 publications

(271 citation statements)

References 141 publications

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“…This presents a major challenge to genomic stability (3)(4)(5)(6) and is implicated in the pathogenesis of multiple human diseases, including cancer and neurodegenerative disorders (7,8). Abundant DNA damage from oxidative stress constitutes ∼10% of all DNA lesions and includes oxidative DNA damage, such as base damage, sugar moiety damage, apurinic/apyrimidinic (AP) sites, DNA single-strand breaks (SSBs), and double-strand breaks (DSBs) (2,6).…”

mentioning

confidence: 99%

APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress

Wallace

Berman

Mueller

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

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The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3′-5′ nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3′-5′ exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.oxidative stress | APE2 | Zf-GRF | crystallography | Xenopus laevis

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mentioning

confidence: 99%

APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress

Wallace

Berman

Mueller

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

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“…In the area of cancer, antioxidants are increasing in importance. Indeed, it has been reported that antioxidants can prevent cancer due to their effects on oxidative stress [17].…”

Section: Discussionmentioning

confidence: 99%

Perfusion of Multiple Micronutrients Supplement of HCC-Invaded Human Liver Reduces Oxidative Stress and Proliferation of Cancer Cells

Piera

Pasquale²,

Anna³

et al. 2016

CRJ

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Administration of the chemotherapeutic agent by organ perfusion is more effective than the systemic administration.The active drug is reached by the tumor, to a higher concentration, and normal tissues are spared from major damages. The perfusion of various areas of the body is a recent goal of the experimental and clinical trials. Fatal malignancies observed in humans occur mainly in the abdominal area of the body, The development of a clinically applicable technique for the perfusion of this area is desirable. This report covers the laboratory studies, carried out in the development of a liver perfusion technique for chemotherapy. The results obtained have allowed us to highlight that, the potential anticancer activity of Citozym, a micronutrients supplement, is likely the result of the inhibition of oxidative stress. This work is the preliminary evidence, of the possible mechanism by which Citozym exerts its antineoplastic activity.

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“…Oxidative stress have been found not only in brain tissues but also in peripheral tissues of individuals affected by PD, mild cognitive impairment (MCI) and other degenerative diseases, including HD, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and others [222]. Therefore, a delicate balance between the levels of oxidants and antioxidants is essential to maintain the optimum levels of ROS [229].…”

Section: Oxidative Stress and Pdmentioning

confidence: 99%

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

Mehan¹,

Kaur²,

Dudi³

et al. 2017

Open J Parkinsons Dis Treatm

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal cell death in the specifi c brain region like basal ganglia, cerebral cortex and hippocampus. Symptoms associated with PD patients are rigidity, akathesia, tremor, postural imbalance, cognitive and memory dysfunctions. Pathological hallmarks are dopaminergic neuronal degeneration, neuro-infl ammation, oxidative stress, free radical generation. In the typical Parkinson's disease model, 6-Hydroxydopamine (6-OHDA) is delivered unilaterally by stereotactic injection into the SNc (substantia nigra pars-compacta) or the striatum mimics the PD symptoms. In addition, it has been shown that 6-OHDA is toxic to complex I & IV of the mitochondrial respiratory chain, leading to subsequent respiratory inhibition and further processed ATP depletion, oxidative stress and neuro-infl ammation. Forskolin (FSK), a diterpene natural plant phytochemical obtained from (Coleus Forskohli), a potent direct activator of adenyl cyclase (AC) enzyme which further activates cAMP/PK A /CREB pathway. FSK mediated activation of AC/cAMP/PK A / CREB pathway is responsible for various neuroprotective mechanisms Based on important and versatile role of FSK, the present study has been designed to investigate the role of cAMP mediated CREB activation in 6-hydroxydopamine induced mitochondrial associated neurotoxicity in rats. Further the studies are extended to understand the disease pathogenesis and to investigate and discuss the various possible central mechanisms involved in the effect of such targets using behavioral paradigm and biochemical markers of neurodegeneration.

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Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer

Cited by 363 publications

References 141 publications

APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress

APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress

Perfusion of Multiple Micronutrients Supplement of HCC-Invaded Human Liver Reduces Oxidative Stress and Proliferation of Cancer Cells

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

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