Epigenetički lijekovi u medicini

master's thesis

• Title (english): Epigenetic drugs in medicine
• Author: Rosana Rađan
• Mentor: Ana Katušić (mentor)
• Committee member: Floriana Jakuš (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Ana Katušić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2019-09-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Cytology

Abstract

Prefiks epi- na grčkom znači „iznad“. Doslovni prijevod je „iznad genoma“. Epigenetika obuhvaća sve procese koji reguliraju DNA bez promjene njene sekvence. Naime u ljudskom tijelu postoji preko 200 različitih vrsta diferenciranih stanica, a sve one dijele isti genom. Ono što povezuje stanični genotip i fenotip su epigenetski mehanizmi kojima se odlučuje koji su geni i u kolikoj mjeri izraženi ili utišani.
Cilj ovog diplomskog rada je obraditi osnovne mehanizme epigenetike. Navedeni su osnovni epigenetički mehanizmi regulacije genske ekspresije kao što su DNA metilacija, histonske modifikacije i RNA interferencija, ali bitno je napomenuti da nisu jedini. To je razlog što je epigenetika danas jedno od najbrže rastućih polja u biologiji. Njena široka uloga u biološkim procesima čini je izuzetno bitnom u patofiziologiji bolesti. Sukladno tome, epigenetički patofiziološki mehanizmi prisutni su u bolestima iz mnogih područja onkologije, neurologije, psihijatrije, imunologije, embriologije, itd. Za znanstvenike je posebno zanimljivo istraživati epigenetičke promjene u bolestima koje su klinički izazovne kao npr. bolesti multifaktorijalnog porijekla te bolesti čije je liječenje na bilo koji način ograničeno. Zapravo epigenetički važni proteini i molekularnih puteva istražuju se u svrhu pronalaska novih meta i metoda liječenja. FDA (engl. Food and Drug Administration) je zasad odobrila epigenetičke lijekove koji spadaju pod skupinu inhibitora enzima HDAC i DNMT. Ti se lijekovi nazivaju još i lijekovi „prve generacije“, no u skorijoj budućnosti se očekuje i porast novoodobrenih lijekova, posebno onih koji koriste mehanizam RNA interferencije.

Abstract (english)

The “epi” prefix means "above in Greek." The literal translation of this prefix is "above the genome". Epigenetics encompasses processes that regulate DNA without changing its sequence. Specifically, there are over 200 different types of differentiated cells in the human body, all of which share the same genome. What links the cell genotype and the phenotype are the epigenetic mechanisms that decide which genes are active and to which extent they are expressed or silenced.
The aim of this thesis is to explain the basic mechanisms of epigenetics. Basic epigenetic mechanisms for gene expression regulation, such as DNA methylation, histone modifications, and RNA interference, are outlined in this thesis, but it is important to note that they are not the only ones. This is why epigenetics is one of the fastest growing fields in modern biology. Its broad role in biological processes makes it extremely important in the pathophysiology of the disease. Accordingly, epigenetic pathophysiological mechanisms are present in diseases of many areas of oncology, neurology, psychiatry, immunology, embryology, etc. It is particularly interesting for scientists to investigate epigenetic changes in clinically challenging diseases, such as those of multifactorial origin and diseases of which treatment is limited in any way. In fact, epigenetically important proteins and molecular pathways have been studied aiming to find new targets and methods of treatment. So far FDA (Food and Drug Administration) had approved epigenetic drugs that are HDAC and DNMT enzyme inhibitors. These drugs are also called "first generation" drugs, but an increase in newly approved drugs is expected in the near future, especially those with the RNA interference activity.

• Keywords: epigenetika; metilacija DNA; histonske modifikacije; RNA interferencija; DNMTi; HDACi
• Keywords (english): epigenetics; DNA methylation; histone modifications; RNA interference; DNMTi; HDACi
• Language: croatian
• URN:NBN: urn:nbn:hr:105:517812
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-02-25 08:08:38