Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey

Emerging studies reveal that neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are commonly linked to DNA damage accumulation and repair deficiency. Neurons are particularly vulnerable to DNA damage due to their high metabolic activity, relying primarily on oxidative phosphorylation, which leads to increased reactive oxygen species (ROS) generation and subsequent DNA damage. Efficient and timely repair of such damage is critical for guarding the integrity of genomic DNA and for cell survival. Several genes predominantly associated with RNA/DNA metabolism have been implicated in both ALS and FTD, suggesting that the two diseases share a common underlying pathology with varied clinical manifestations. Recent studies reveal that many of the gene products, including RNA/DNA binding proteins (RBPs) TDP-43 and FUS are involved in diverse DNA repair pathways. A key question in the etiology of the ALS/FTD spectrum of neurodegeneration is the mechanisms and pathways involved in genome instability caused by dysfunctions/mutations of those RBP genes and their consequences in the central nervous system. The understanding of such converging molecular mechanisms provides insights into the underlying etiology of the rapidly progressing neurodegeneration in ALS/FTD, while also revealing novel DNA repair target avenues for therapeutic development. In this review, we summarize the common mechanisms of neurodegeneration in ALS and FTD, with a particular emphasis on the DNA repair defects induced by ALS/FTD causative genes. We also highlight the consequences of DNA repair defects in ALS/FTD and the therapeutic potential of DNA damage repair-targeted amelioration of neurodegeneration.

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The sensitivity of DNA damage response target ovarian gap junction proteins in granulosa cells in women with advanced endometriosis

10.26226/morressier.5af300af738ab10027aa9538 ◽

2018 ◽

Author(s):

Ratna Chattopadhyay ◽

Pratip Chakraborty

Keyword(s):

Dna Damage ◽

Gap Junction ◽

Dna Damage Response ◽

Granulosa Cells ◽

Damage Response ◽

Gap Junction Proteins ◽

Junction Proteins ◽

Response Target

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EFFECTS OF LIPOPOLYSACCHARIDEINDUCED ENDOTOXEMIA ON OOCYTE MEIOTIC MATURATION, DNA DAMAGE AND VIABILITY OF OVARIAN GRANULOSA CELLS IN MICE

Proceedings of the III International Conference on Biology and Medical Sciences: Innovations and practice ◽

10.29013/iii-conf-med-pp-3-35-41 ◽

2018 ◽

Author(s):

O. Kondratska ◽

N. Grushka ◽

N. Makogon ◽

S. Pavlovych ◽

R. Yanchii

Keyword(s):

Dna Damage ◽

Granulosa Cells ◽

Meiotic Maturation ◽

Ovarian Granulosa Cells ◽

Oocyte Meiotic Maturation

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TRDMT1 Participates in the DNA Damage Repair of Granulosa Cells in Premature Ovarian Failure

SSRN Electronic Journal ◽

10.2139/ssrn.3705274 ◽

2020 ◽

Author(s):

Chunli Sha ◽

Lu Chen ◽

Li Lin ◽

Taoqiong Li ◽

Hong Wei ◽

...

Keyword(s):

Dna Damage ◽

Granulosa Cells ◽

Premature Ovarian Failure ◽

Dna Damage Repair ◽

Ovarian Failure ◽

Damage Repair

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DNA Damage and Repair in the Brain After Cerebral Ischemia

Current Topics in Medicinal Chemistry ◽

10.2174/1568026013394688 ◽

2001 ◽

Vol 1 (6) ◽

pp. 483-495 ◽

Cited By ~ 13

Author(s):

Bentham Science Publisher Philip K. Liu

Keyword(s):

Dna Damage ◽

Cerebral Ischemia ◽

Dna Damage And Repair ◽

The Brain

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Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03369-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ding-fang Zhang ◽

Zhi-chun Yang ◽

Jian-qiang Chen ◽

Xiang-xiang Jin ◽

Yin-da Qiu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Dna Damage ◽

Cell Adhesion ◽

Anticancer Activity ◽

Cancer Cells ◽

Castration Resistant Prostate Cancer ◽

Prostate Cancer Cells ◽

Dna Damage And Repair ◽

Castration Resistant

Abstract Background Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. Methods The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), β-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. Results The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. Conclusion Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

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