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Molecular Targets and Repositioned Drugs For the Treatment of Post Traumatic Stress Disorder (PTSD)

Year 2023, , 532 - 546, 03.05.2023

Elıf Kubat Oktem

https://doi.org/10.35414/akufemubid.1173072

Abstract

Post-traumatic stress disorder (PTSD) is a mental illness caused by trauma following an accident
involving physical injury or by mental shock such as anxiety. Although it is common in the population,
the prognosis and optimal therapies for PTSD are limited. Because the molecular targets for early
intervention remain unclear, a better understanding of the molecular basis of the pathogenesis of PTSD
is essential to address the challenges of disease prognosis and to diagnose and treat these molecular
targets. In this study, performed by processing and analyzing microarray data from two different tissues
of mice exposed to stress, genes with differential expression for the two tissue types were identified,
the signaling pathways in which these genes are enriched were found, the protein-protein interaction
networks of these genes and the hub proteins in these networks were determined. As a result of
comparing the drug repositioning studies performed separately for the two different tissue types to
reverse the effects of differentially expressed genes, vorinostat, homoharringtonine, and QL-XII -47
were proposed as novel drugs for the treatment of PTSD. Vorinostat, one of these drugs, was also found
to target HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC8 genes in the cell.

Keywords

PTSD systems biology drug repositioning Bioinformatics

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Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar

Year 2023, , 532 - 546, 03.05.2023

Elıf Kubat Oktem

https://doi.org/10.35414/akufemubid.1173072

Abstract

Travma sonrası stres bozukluğu (TSSB), fiziksel hasar veya kaygı gibi zihinsel şok içeren bir kazayı takiben
görülen travmanın neden olduğu zihinsel bir hastalıktır. Toplumda yaygın olmasına rağmen, TSSB'nin
prognozu ve optimal terapötikleri sınırlıdır. Erken müdahale için moleküler hedefler belirsiz kaldığından,
daha iyi bir TSSB patogenezinin moleküler temellerinin anlaşılması hastalık prognozunun zorluklarını
karşılamak ve bu moleküler hedeflere yönelik teşhis ve tedavi için gereklidir. Strese maruz bırakılan
farelerin iki farklı dokusundan elde edilen mikrodizi verilerinin işlenmesi ve analiziyle yapılan bu
çalışmada, her iki tip doku için de anlatımı farklılık gösteren genler tespit edilmiş, bu genlerin
zenginleştiği yolizleri bulunmuş, bu genlerin protein protein etkileşim ağları ve bu ağlardaki hub
proteinler tespit edilmiştir. Bu hastalıkta anlatımı farklılık gösteren genlerin etkilerini tersini çevirmeye
yönelik her iki farklı tip doku için de ayrı ayrı yapılan ilaç yeniden konumlandırma çalışmalarının
karşılaştırılması sonucunda; vorinostat, homoharringtonin ve QL-XII-47 TSSB’yi iyileştirmek için yeni ilaç
adayları olarak önerilmiştir. Bu ilaçlardan vorinostat’ın, hücrede HDAC1, HDAC2, HDAC3, HDAC6, HDAC7
ve HDAC8 genlerini hedef aldığı tespit edilmiştir.

Keywords

TSSB Travma sonrası stres bozukluğu biyoinformatik ilaç yeniden konumlandırma sistem biyolojisi

References

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  • Albrechet-Souza, L., Carvalho, M. C., and Brandão, M. L. (2013). D1-like receptors in the nucleus accumbens shell regulate the expression of contextual fear conditioning and activity of the anterior cingulate cortex in rats. International Journal of Neuropsychopharmacology, 16(5), 1045–1057. https://doi.org/10.1017/S146114571200082X
  • Alvandi, F., Kwitkowski, V. E., Ko, C. W., Rothmann, M. D., Ricci, S., Saber, H., Ghosh, D., Brown, J., Pfeiler, E., Chikhale, E., Grillo, J., Bullock, J., Kane, R., Kaminska, E., Farrell, A. T., and Pazdur, R. (2014). U.S. food and drug administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia. Oncologist, 19, 94–99.
  • Antoniadis, E. A., and McDonald, R. J. (2006). Fornix, medial prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus: Roles in a fear-based context discrimination task. Neurobiology of Learning and Memory, 85(1), 71–85. https://doi.org/10.1016/j.nlm.2005.08.011
  • Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., and Sherlock, G. (2000). Gene ontology: Tool for the unification of biology. In Nature Genetics (Vol. 25, Issue 1, pp. 25–29). https://doi.org/10.1038/75556
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  • Bahari-Javan, S., Sananbenesi, F., and Fischer, A. (2014). Histone-acetylation: a link between Alzheimer's disease and post-traumatic stress disorder?. Frontiers in neuroscience, 8, 160. https://doi.org/10.3389/fnins.2014.00160
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  • Belzung, C., Turiault, M., and Griebel, G. (2014). Optogenetics to study the circuits of fear- and depression-like behaviors: a critical analysis. Pharmacology, biochemistry, and behavior, 122, 144–157. https://doi.org/10.1016/j.pbb.2014.04.002
  • Bisson, J. I., Roberts, N. P., Andrew, M., Cooper, R., and Lewis, C. (2013). Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults. The Cochrane database of systematic reviews, 2013(12), CD003388. https://doi.org/10.1002/14651858.CD003388.pub4
  • Carbon, S., Douglass, E., Good, B. M., Unni, D. R., Harris, N. L., Mungall, C. J., Basu, S., Chisholm, R. L., Dodson, R. J., Hartline, E., Fey, P., Thomas, P. D., Albou, L. P., Ebert, D., Kesling, M. J., Mi, H., Muruganujan, A., Huang, X., Mushayahama, T., … Elser, J. (2021). The Gene Ontology resource: Enriching a GOld mine. Nucleic Acids Research, 49(D1),D325–D334. https://doi.org/10.1093/nar/gkaa1113
  • Chen, Y. T., Xie, J. Y., Sun, Q., and Mo, W. J. (2019). Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking. International Journal of Oncology, 54(1), 152–166. https://doi.org/10.3892/ijo.2018.4618
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There are 55 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Elıf Kubat Oktem 0000-0003-0913-8527

Early Pub Date April 28, 2023
Publication Date May 3, 2023
Submission Date September 9, 2022
Published in Issue Year 2023

Cite

APA Kubat Oktem, E. (2023). Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 23(2), 532-546. https://doi.org/10.35414/akufemubid.1173072
AMA Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. May 2023;23(2):532-546. doi:10.35414/akufemubid.1173072
Chicago Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23, no. 2 (May 2023): 532-46. https://doi.org/10.35414/akufemubid.1173072.
EndNote Kubat Oktem E (May 1, 2023) Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23 2 532–546.
IEEE E. Kubat Oktem, “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 23, no. 2, pp. 532–546, 2023, doi: 10.35414/akufemubid.1173072.
ISNAD Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23/2 (May 2023), 532-546. https://doi.org/10.35414/akufemubid.1173072.
JAMA Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2023;23:532–546.
MLA Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 23, no. 2, 2023, pp. 532-46, doi:10.35414/akufemubid.1173072.
Vancouver Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2023;23(2):532-46.


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