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

Yıl 2023, Cilt: 23 Sayı: 2, 532 - 546, 03.05.2023

Elıf Kubat Oktem

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

Öz

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.

Anahtar Kelimeler

PTSD, systems biology, drug repositioning, Bioinformatics

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

Öz

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.

Anahtar Kelimeler

TSSB, Travma sonrası stres bozukluğu, biyoinformatik, ilaç yeniden konumlandırma, sistem biyolojisi

Kaynakça

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