Charcot-Marie-Tooth hastalığının tedavisi için yeni ilaç moleküllerinin araştırılması /
Yazar: GİZEM TUNA
Danışman: DR. ÖĞR. ÜYESİ VİLDAN ENİSOĞLU ATALAY
Üsküdar Üniversitesi / Fen Bilimleri Enstitüsü / Biyomühendislik Ana Bilim Dalı / Biyoteknoloji Bilim Dalı
Derece: Yüksek Lisans, 2020
Konu: Biyokimya = Biochemistry ; Biyoteknoloji = Biotechnology ; Kimya = Chemistry
Dizin: CMT =   ; DNA = DNA ; DNA onarım testi = DNA repair test ; Nöroleptik ilaçlar =   ; Organik moleküller = Organic molekules ; RNA = RNA ; dsRNA = dsRNA

Özet:
Charcot Marie Tooth (CMT), kalıtsal bir hastalık olmakla beraber diğer nörolojik bulgulara sahip ve hayat kalitesini düşüren aynı zamanda beyni etkileyen hastalıklardan biraz daha farklıdır. Periferik nöropati hastalık olan CMT, çevresel sinir hasarına sebebiyet vermektedir. Belirti ve nörofizyolojik bulgular için nöroloji uzmanlığında teşhis edilebilmektedir ve gerekli durum ve koşullarda nöropataloji uzmanlığının desteği alınır. CMT'de çok fazla gen yer alır ve miyelinasyon, Schwann hücre farklılaşması, sinyal transdüksiyonu, protein translasyonu ve tek iplikli DNA kırılma onarımındaki yolları içerir. Genetik bilginin bolluğu, genetik testlere rasyonel bir yaklaşım gerektirmektedir.
Son yıllarda CMT'nin kesin bir tedavisi olmadığı gibi, hastalık üzerinde klinik olarak denenmiş fakat olumlu sonuç vermemiş birçok ilaç bulunmaktadır. Bunun yanı sıra CMT için semptomları ağırlaştıran ve hastalığı daha da gerileten bazı ilaç çeşitleri tespit edilmiştir.  Hastalık yapan genler ile bu ilaçların arasındaki bağlantıyı in siliko yöntemler ile kenetlenme çalışması yapıp anlamlandırmaya çalışarak risk faktörü çıkan ilaçların neden negatif etkiye sebep olduğu saptanmaya çalışılacaktır.
Hastalar üzerinde kullanılmaması gereken risk faktörü ilaçlar derlememizde mevcut olup, CMT hastalarının yaşam kalitesini arttırabilmek için denenmiş çeşitli ilaçlara yanıt vermeyen ya da tam anlamıyla iyileştirme gözlemleyemediğimiz hastalıkta, hastalık proteinlerine kenetleme çalışması yaparak daha önce kullanılmış ilaçlar ve yeni aday ilaç molekülleri ile güçlü etkileşime giren amino asitlerin tespitiyle birlikte bağlanma enerjileri de hesaplanarak olası yeni moleküllerin belirlenmesi hedeflenmektedir.

Abstract:
Although Charcot Marie Tooth (CMT) is an inherited disease, it is slightly different from other diseases that have neurological symptoms and reduce the quality of life and affect the brain.CMT, a peripheral neuropathy disease, is an autosomal dominant disease and causes peripheral nerve damage.There are too many genes involved in CMT hereditary disease and includes pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation, and single-stranded DNA breakage repair. The abundance of genetic information requires a rational approach to genetic testing. CMT is one of the genetic conditions in which molecular-based treatments are progressing to the clinical trial stage. 
For symptoms and neurophysiological findings, it can be diagnosed in the neurology specialty and the support of the neuropathology expertise is received in the necessary conditions and conditions. In recent years, CMT does not have a definitive treatment, and there are many drugs that have been clinically tested on the disease but have not yielded positive results. In addition, some drug types have been identified for CMT that aggravate symptoms and further regress the disease. By trying to make sense of the connection between disease-causing genes and these drugs with in silico methods, it will be tried to determine why drugs with risk factors cause negative effects.
Risk factor drugs that should not be used on patients are available in our compilation. In the disease that does not respond to various drugs that have been tried to increase the quality of life of CMT patients or we cannot observe a complete improvement, the disease proteins are coupled with previously used drugs and amino acids that interact strongly with new candidate drug molecules. With the determination, it is aimed to determine possible new molecules by calculating the binding energies.
Although Charcot Marie Tooth (CMT) is an inherited disease, it is slightly different from other diseases that have neurological findings and reduce the quality of life and also affect the brain. CMT, a peripheral neuropathy disease, causes peripheral nerve damage. For symptoms and neurophysiological findings, it can be diagnosed in the neurology specialty and the support of the neuropathology expertise is received in the necessary conditions and conditions. There are many genes involved in CMT and include pathways in myelination, Schwann cell differentiation, signal transduction, protein translation, and single-stranded DNA breakage repair. The abundance of genetic information requires a rational approach to genetic testing.
In recent years, CMT does not have a definitive treatment, and there are many drugs that have been clinically tested on the disease but have not yielded positive results. In addition, some drugs have been identified for CMT that aggravate symptoms and further regress the disease. By trying to make sense of the connection between disease-causing genes and these drugs with in-silico methods, it will be tried to determine why drugs with risk factors cause negative effects.
Risk factor drugs that should not be used on patients are available in our compilation, and in the disease that does not respond to various drugs that have been tried to increase the quality of life of CMT patients or we cannot observe a full improvement, the disease proteins are coupled with previously used drugs and amino acids that interact strongly with new candidate drug molecules. With the determination, it is aimed to determine possible new molecules by calculating the binding energies