The effect of FOXO gene family variants and global DNA metylation on RRMS disease

Edgünlü, Tuba Gökdoğan; Ünal, Yasemin; Çelik, Sevim; Genç, Öyküm; Emre, Ufuk; Kutlu, Gülnihal

doi:10.1016/j.gene.2019.144172

Cited by 15 publications

(12 citation statements)

References 20 publications

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“…Clark et al highlighted important mechanisms of DNA methylation in RA and the wider context of immune dysregulation ( Clark et al, 2020 ). Prior studies identified aberrant expression of apoptosis and DNA damage regulatory genes in MS, suggesting that DNA methylation may be effective in neuronal loss in RRMS ( Gökdoǧan Edgünlü et al, 2020 ). Consistent with previous studies, MSH5 might contribute to the pathogenesis of NMOSD.…”

Section: Discussionmentioning

confidence: 99%

Multi-Level Analyses of Genome-Wide Association Study to Reveal Significant Risk Genes and Pathways in Neuromyelitis Optica Spectrum Disorder

et al. 2021

Front. Genet.

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BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system and it is understandable that environmental and genetic factors underlie the etiology of NMOSD. However, the susceptibility genes and associated pathways of NMOSD patients who are AQP4-Ab positive and negative have not been elucidated.MethodsSecondary analysis from a NMOSD Genome-wide association study (GWAS) dataset originally published in 2018 (215 NMOSD cases and 1244 controls) was conducted to identify potential susceptibility genes and associated pathways in AQP4-positive and negative NMOSD patients, respectively (132 AQP4-positive and 83 AQP4-negative).ResultsIn AQP4-positive NMOSD cases, five shared risk genes were obtained at chromosome 6 in AQP4-positive NMOSD cases by using more stringent p-Values in both methods (p < 0.05/16,532), comprising CFB, EHMT2, HLA-DQA1, MSH5, and SLC44A4. Fifty potential susceptibility gene sets were determined and 12 significant KEGG pathways were identified. Sixty-seven biological process pathways, 32 cellular-component pathways, and 29 molecular-function pathways with a p-Value of <0.05 were obtained from the GO annotations of the 128 pathways identified. In the AQP4 negative NMOSD group, no significant genes were obtained by using more stringent p-Values in both methods (p < 0.05/16,485). The 22 potential susceptibility gene sets were determined. There were no shared potential susceptibility genes between the AQP4-positive and negative groups, furthermore, four significant KEGG pathways were also identified. Of the GO annotations of the 165 pathways identified, 99 biological process pathways, 37 cellular-component pathways, and 29 molecular-function pathways with a p-Value of <0.05 were obtained.ConclusionThe potential molecular mechanism underlying NMOSD may be related to proteins encoded by these novel genes in complements, antigen presentation, and immune regulation. The new results may represent an improved comprehension of the genetic and molecular mechanisms underlying NMOSD.

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Section: Discussionmentioning

confidence: 99%

Multi-Level Analyses of Genome-Wide Association Study to Reveal Significant Risk Genes and Pathways in Neuromyelitis Optica Spectrum Disorder

et al. 2021

Front. Genet.

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“…For example, central nervous system myelination involving oligodendrocyte progenitor cells is believed to be controlled through FoxO1 transcription factors [200] that may impact disease such as multiple sclerosis [201]. Other work suggests that progressive pathology of demyelinating disorders may be tied to epigenetic changes with DNA methylation and involve genetic variations of FoxO3a and FoxO1 [202]. FoxO activation during autophagy can be beneficial to cell survival, suggesting that a fine balance in FoxO activity may be required to promote cellular protection and survival.…”

Section: Circadian Clock Genes and The Silent Mating Type Information Regulation 2 Homolog 1 (Saccharomyces Cerevisiae) (Sirt1)mentioning

confidence: 99%

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

Maiese

2021

Biomolecules

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Neurodegenerative disorders affect fifteen percent of the world’s population and pose a significant financial burden to all nations. Cognitive impairment is the seventh leading cause of death throughout the globe. Given the enormous challenges to treat cognitive disorders, such as Alzheimer’s disease, and the inability to markedly limit disease progression, circadian clock gene pathways offer an exciting strategy to address cognitive loss. Alterations in circadian clock genes can result in age-related motor deficits, affect treatment regimens with neurodegenerative disorders, and lead to the onset and progression of dementia. Interestingly, circadian pathways hold an intricate relationship with autophagy, the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), and the trophic factor erythropoietin. Autophagy induction is necessary to maintain circadian rhythm homeostasis and limit cortical neurodegenerative disease, but requires a fine balance in biological activity to foster proper circadian clock gene regulation that is intimately dependent upon mTOR, SIRT1, FoxOs, and growth factor expression. Circadian rhythm mechanisms offer innovative prospects for the development of new avenues to comprehend the underlying mechanisms of cognitive loss and forge ahead with new therapeutics for dementia that can offer effective clinical treatments.

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“…FoxO1 transcription factors [ 256 ] oversee the myelination of nerves that requires oligodendrocyte progenitor cells and determine the progression of disorders that include multiple sclerosis [ 257 ]. Additional studies indicate that epigenetic changes in DNA methylation and genetic variations of FoxO3a and FoxO1 also can affect demyelinating disorders [ 258 ]. Yet, it is important to state that a fine balance in FoxO activity is necessary to lead to the protection of cells since activation of FoxOs with autophagy can be beneficial.…”

Section: Mammalian Forkhead Transcription Factors (Foxos)mentioning

confidence: 99%

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Maiese

2021

Front. Biosci. (Landmark Ed)

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Introduction 3. Biological clocks and circadian rhythm pathways for dementia treatment 4. Circadian rhythm disruption and the wingless wnt pathway 5. The mechanistic target of rapamycin (mTOR) and autophagy 6. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) 7. Mammalian forkhead transcription factors (FoxOs) 8. Future perspectives 9. Author contributions 10. Ethics approval and consent to participate 11. Acknowledgment 12. Funding 13. Conflict of interest 14. References

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The effect of FOXO gene family variants and global DNA metylation on RRMS disease

Cited by 15 publications

References 20 publications

Multi-Level Analyses of Genome-Wide Association Study to Reveal Significant Risk Genes and Pathways in Neuromyelitis Optica Spectrum Disorder

Multi-Level Analyses of Genome-Wide Association Study to Reveal Significant Risk Genes and Pathways in Neuromyelitis Optica Spectrum Disorder

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

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