Epigenetic Modifications: A Therapeutic Approach in Alzheimer's Disease
DOI:
https://doi.org/10.47611/jsrhs.v13i4.7924Keywords:
Alzheimer's Disease, Epigenetics, Therapy, DNA Methylation, Histone Modifications, Non-Coding RNAs, Epigenetic MechanismsAbstract
Alzheimer’s disease is a progressive neurodegenerative disease that has affected millions of people worldwide, marked by memory loss and cognitive deficits. Currently, treatments only attempt to alleviate symptoms rather than reversing neuronal damage or cognitive deficits. However, epigenetic therapies correlated with their subsequent epigenetic modifications have been shown to show potential in pre-clinical trials, prompting researchers to focus more on this subject matter. By examining many credible sources, this paper aims to highlight potential epigenetic modifications in Alzheimer’s disease patients and shed light on their subsequent epigenetic therapy. Ultimately, many pre-clinical trials have reiterated the potential these therapies have for reversing Alzheimer’s disease pathology and progression. The three primary epigenetic therapies highlighted include DNA methylation inhibitors, histone deacetylase (HDAC) inhibitors, and non-coding RNA-based therapies. Altogether, with further advances in pre-clinical trials and a transition into human clinical trials, the potential of these therapies can be utilized as a novel approach to reversing the damage that occurs from epigenetic modifications in Alzheimer’s patients.
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References or Bibliography
Alzheimer's disease facts and figures. (2024). Alzheimer's & dementia : the journal of the Alzheimer's Association, 20(5), 3708–3821. https://doi.org/10.1002/alz.13809
Afzal, O., Dalhat, M. H., Altamimi, A. S. A., Rasool, R., Alzarea, S. I., Almalki, W. H., Murtaza, B. N., Iftikhar, S., Nadeem, S., Nadeem, M. S., & Kazmi, I. (2022). Green Tea Catechins Attenuate Neurodegenerative Diseases and Cognitive Deficits. Molecules (Basel, Switzerland), 27(21), 7604. https://doi.org/10.3390/molecules27217604
Banzhaf-Strathmann, J., Benito, E., May, S., Arzberger, T., Tahirovic, S., Kretzschmar, H., Fischer, A., & Edbauer, D. (2014). MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease. The EMBO journal, 33(15), 1667–1680. https://doi.org/10.15252/embj.201387576
Beech, T. (2023). DNA methylation in Alzheimer’s Disease: A mechanism, biomarker, and potential therapeutic target. Biomodal. https://biomodal.com/blog/dna-methylation-in-alzheimers-disease/
Bufill, E., Ribosa-Nogué, R., & Blesa, R. (2020). The therapeutic potential of epigenetic modifications in Alzheimer’s disease. In X. Huang (Ed.), Alzheimer’s disease: Drug discovery (Chap. 9). Exon Publications. https://doi.org/10.36255/exonpublications.alzheimersdisease.2020.ch9
Bushati, N., & Cohen, S. M. (2007). microRNA functions. Annual review of cell and developmental biology, 23, 175–205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
Dong, X., & Weng, Z. (2013). The correlation between histone modifications and gene expression. Epigenomics, 5(2), 113–116. https://doi.org/10.2217/epi.13.13
Faghihi, M. A., Modarresi, F., Khalil, A. M., Wood, D. E., Sahagan, B. G., Morgan, T. E., Finch, C. E., St Laurent, G., 3rd, Kenny, P. J., & Wahlestedt, C. (2008). Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nature medicine, 14(7), 723–730. https://doi.org/10.1038/nm1784
Gao, X., Chen, Q., Yao, H., Tan, J., Liu, Z., Zhou, Y., & Zou, Z. (2022). Epigenetics in Alzheimer's Disease. Frontiers in aging neuroscience, 14, 911635. https://doi.org/10.3389/fnagi.2022.911635
Gräff, J., Tsai, LH. Histone acetylation: molecular mnemonics on the chromatin. Nat Rev Neurosci 14, 97–111 (2013). https://doi.org/10.1038/nrn3427
Janczura, K. J., Volmar, C.-H., Sartor, G. C., Rao, S. J., Ricciardi, N. R., Lambert, G., Brothers, S. P., & Wahlestedt, C. (2018). Inhibiting HDAC3 reverses Alzheimer’s disease-related pathologies in a mouse model. Proceedings of the National Academy of Sciences, 115(47). https://doi.org/10.1073/pnas.1805436115
Jang, H. S., Shin, W. J., Lee, J. E., & Do, J. T. (2017). CpG and Non-CpG Methylation in Epigenetic Gene Regulation and Brain Function. Genes, 8(6), 148. https://doi.org/10.3390/genes8060148
Kaur, G., Rathod, S. S. S., Ghoneim, M. M., Alshehri, S., Ahmad, J., Mishra, A., & Alhakamy, N. A. (2022). DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders. Biology, 11(1), 90. https://doi.org/10.3390/biology11010090
Kim, H. J., & Bae, S. C. (2011). Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. American journal of translational research, 3(2), 166–179.
Klein, H. U., McCabe, C., Gjoneska, E., Sullivan, S. E., Kaskow, B. J., Tang, A., Smith, R. V., Xu, J., Pfenning, A. R., Bernstein, B. E., Meissner, A., Schneider, J. A., Mostafavi, S., Tsai, L. H., Young-Pearse, T. L., Bennett, D. A., & De Jager, P. L. (2019). Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer's human brains. Nature neuroscience, 22(1), 37–46. https://doi.org/10.1038/s41593-018-0291-1
Lan, Z., Chen, Y., Jin, J., Xu, Y., & Zhu, X. (2022). Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease. Frontiers in molecular neuroscience, 14, 821002. https://doi.org/10.3389/fnmol.2021.821002
Lobanov-Rostovsky, S., He, Q., Chen, Y., Liu, Y., Wu, Y., Liu, Y., Venkatraman, T., French, E., Curry, N., Hemmings, N., Bandosz, P., Chan, W. K., Liao, J., & Brunner, E. J. (2023). Growing old in China in socioeconomic and epidemiological context: Systematic review of social care policy for older people. BMC Public Health, 23(1), 1272. https://doi.org/10.1186/s12889-023-15583-1
Ma, P., Li, Y., Zhang, W., Fang, F., Sun, J., Liu, M., Li, K., & Dong, L. (2019). Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease. Current Alzheimer research, 16(7), 596–612. https://doi.org/10.2174/1567205016666190725130134
National Library of Medicine. (2021). APOE gene: Medlineplus genetics. MedlinePlus. https://medlineplus.gov/genetics/gene/apoe/
National Library of Medicine. (2021). What is epigenetics? MedlinePlus. https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/
Nativio, R., Donahue, G., Berson, A., Lan, Y., Amlie-Wolf, A., Tuzer, F., Toledo, J. B., Gosai, S. J., Gregory, B. D., Torres, C., Trojanowski, J. Q., Wang, L. S., Johnson, F. B., Bonini, N. M., & Berger, S. L. (2018). Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease. Nature neuroscience, 21(4), 497–505. https://doi.org/10.1038/s41593-018-0101-9
Olufunmilayo, E. O., & Holsinger, R. M. D. (2023). Roles of Non-Coding RNA in Alzheimer's Disease Pathophysiology. International journal of molecular sciences, 24(15), 12498. https://doi.org/10.3390/ijms241512498
Payne, A., Nahashon, S., Taka, E., Adinew, G. M., & Soliman, K. F. A. (2022). Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age. Biomolecules, 12(3), 371. https://doi.org/10.3390/biom12030371
Ranganathan, K., & Sivasankar, V. (2014). MicroRNAs - Biology and clinical applications. Journal of oral and maxillofacial pathology : JOMFP, 18(2), 229–234. https://doi.org/10.4103/0973-029X.140762
Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., & Reddy, P. H. (2022). Phosphorylated Tau in Alzheimer's Disease and Other Tauopathies. International journal of molecular sciences, 23(21), 12841. https://doi.org/10.3390/ijms232112841
Ren, R., Qi, J., Lin, S., Liu, X., Yin, P., Wang, Z., Tang, R., Wang, J., Huang, Q., Li, J., Xie, X., Hu, Y., Cui, S., Zhu, Y., Yu, X., Wang, P., Zhu, Y., Wang, Y., Huang, Y., Hu, Y., … Wang, G. (2022). The China Alzheimer Report 2022. General psychiatry, 35(1), e100751. https://doi.org/10.1136/gpsych-2022-100751
Santana, D. A., Smith, M. A. C., & Chen, E. S. (2023). Histone Modifications in Alzheimer's Disease. Genes, 14(2), 347. https://doi.org/10.3390/genes14020347
Sharma, V. K., Mehta, V., & Singh, T. G. (2020). Alzheimer's Disorder: Epigenetic Connection and Associated Risk Factors. Current neuropharmacology, 18(8), 740–753. https://doi.org/10.2174/1570159X18666200128125641
Tecalco-Cruz, A. C., Ramírez-Jarquín, J. O., Alvarez-Sánchez, M. E., & Zepeda-Cervantes, J. (2020). Epigenetic basis of Alzheimer disease. World journal of biological chemistry, 11(2), 62–75. https://doi.org/10.4331/wjbc.v11.i2.62
Vance, K. W., & Ponting, C. P. (2014). Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends in genetics : TIG, 30(8), 348–355. https://doi.org/10.1016/j.tig.2014.06.001
Walgrave, H., Penning, A., Tosoni, G., Snoeck, S., Davie, K., Davis, E., Wolfs, L., Sierksma, A., Mars, M., Bu, T., Thrupp, N., Zhou, L., Moechars, D., Mancuso, R., Fiers, M., Howden, A. J. M., De Strooper, B., & Salta, E. (2023). microRNA-132 regulates gene expression programs involved in microglial homeostasis. iScience, 26(6), 106829. https://doi.org/10.1016/j.isci.2023.106829
Wang, E., Wang, M., Guo, L., Fullard, J. F., Micallef, C., Bendl, J., Song, W., Ming, C., Huang, Y., Li, Y., Yu, K., Peng, J., Bennett, D. A., De Jager, P. L., Roussos, P., Haroutunian, V., & Zhang, B. (2023). Genome-wide methylomic regulation of multiscale gene networks in Alzheimer's disease. Alzheimer's & Dementia, 19(8), 3472-3495. https://doi.org/10.1002/alz.12969
Wang, J., Yu, J. T., Tan, M. S., Jiang, T., & Tan, L. (2013). Epigenetic mechanisms in Alzheimer's disease: implications for pathogenesis and therapy. Ageing research reviews, 12(4), 1024–1041. https://doi.org/10.1016/j.arr.2013.05.003
Wang, Q., Ge, X., Zhang, J., & Chen, L. (2020). Effect of lncRNA WT1-AS regulating WT1 on oxidative stress injury and apoptosis of neurons in Alzheimer's disease via inhibition of the miR-375/SIX4 axis. Aging, 12(23), 23974–23995. https://doi.org/10.18632/aging.104079
Xu, K., Dai, X. L., Huang, H. C., & Jiang, Z. F. (2011). Targeting HDACs: a promising therapy for Alzheimer's disease. Oxidative medicine and cellular longevity, 2011, 143269. https://doi.org/10.1155/2011/143269
Yan, Z. (2024). Can the damage of Alzheimer’s be undone? University at Buffalo. https://www.buffalo.edu/how/articles.host.html/content/shared/www/eub/here-is-how/Alzheimers.detail.html?utm_source=Flipboard&%3Butm_medium=PromotedStories-Alzheimers-NY&%3Butm_campaign=FM-Reputation-Spring19&%3Butm_content=
Zhang, M., Wang, W., Ye, Q., Fu, Y., Li, X., Yang, K., Gao, F., Zhou, A., Wei, Y., Tian, S., Li, S., Wei, F., Shi, W., & Li, W. D. (2024). Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer's disease mouse model by regulating the expression of APP secretases. Alzheimer's research & therapy, 16(1), 15. https://doi.org/10.1186/s13195-024-01384-0
Zhang, Y., Zhang, Z., Li, L., Xu, K., Ma, Z., Chow, H.-M., Herrup, K., & Li, J. (2020). Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease. The FASEB Journal, 34(12), 16364–16382. https://doi.org/10.1096/fj.202001271R
Zhang, Y., Zhao, Y., Ao, X., Yu, W., Zhang, L., Wang, Y., & Chang, W. (2021). The Role of Non-coding RNAs in Alzheimer's Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers. Frontiers in aging neuroscience, 13, 654978. https://doi.org/10.3389/fnagi.2021.654978
Zhou, Q., Xiong, Y., Qu, B., Bao, A., & Zhang, Y. (2021). DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?. Frontiers in immunology, 12, 738962. https://doi.org/10.3389/fimmu.2021.738962
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