Epigenetika helburu duten sendagaiak

Abstract

“Epigenetics” refers to any change in genetic activity without altering DNA sequence. Non-genetic factors (i.e. infections and drugs) may cause epigenetic alterations throughout our genome, indicating which gene will be expressed and which one will not. Therefore, epigenetics is the linker between genetics and environmental factors and experiences. Exposure to non-genetic factors at crucial stages of development (fetal development, early childhood and adolescence), would establish our epigenome through 3 mechanisms: DNA methylation, post-translational histone modifications and non-coding RNA. There have been many studies in the field of epigenetics in the last decades, the most studied epigenetic mechanism being posttranslational histone acetylation. Alterations on histone acetylation pattern have been related to the development of many diseases. The most notable example is cancer. Based on this, histone deacetylase inhibitors (HDACi) became new targets in oncological therapy. Nowadays, four HDACi are approved for the treatment of different types of cancer, and more than 20 HDACi are being evaluated in clinical phase. The efficacy of HDACi against cancer has leveraged the study of HDACi in other diseases. Due to the complexity and the lack of effective treatment for neurological and psychiatric disorders, HDACi drugs have become an interesting potential therapy. Due to neuroprotective properties of HDACi agents, their effectiveness against Huntington´s and Parkinson’s diseases is being evaluated. HDACi research around bipolar disorder and schizophrenia is also moving forward.; Epigenetika hitzak DNA-sekuentzia aldatu gabe aktibitate genetikoan gertatzen den edozein aldaketari egiten dio erreferentzia. Faktore ez-genetikoek (hala nola, infekzioak eta farmakoak) aldaketa epigenetikoak eragin ditzakete, gure genoma osotik zein gene adieraziko diren eta zein ez erabakiz. Hortaz, epigenetika genetikaren eta inguruko faktoreen eta esperientzien arteko lokailua da. Garai erabakigarrietan (garapen fetalean, haurtzaro goiztiarrean eta nerabetasunean) eraginez, faktore ez-genetikoek gure epigenoma ezarriko lukete, deskribatu izan diren 3 mekanismoren bidez: DNAren metilazioa, histonen itzulpen osteko aldaketak eta RNA ez-kodetzaileen eragina. Azken hamarkadetan, epigenetikaren inguruko ikerketa ugari egin dira; gehien aztertu den mekanismo epigenetikoa itzulpen osteko histonen azetilazioa izan da. Azetilazio-asaldurak hainbat gaixotasunen garapenarekin erlazionatu dira. Horren adibiderik aipagarriena minbizia izan da. Horretan oinarrituz, histonen deazetilasen inhibitzaileak (HDACi) minbiziaren kontrako tratamendu gisa postulatu ziren. Gaur egun, lau HDACi daude onartuta minbizi-mota ezberdinen aurkako tratamendurako, eta 20 baino gehiago fase klinikoan ebaluatzen ari dira. HDACi-ek minbizian duten eraginkortasunak beste gaixotasun batzuetan aztertzeko aukera eman du. Gaixotasun neuroendeka- tzaile eta psikiatrikoen konplexutasuna eta tratamendu eraginkorren falta dela eta, HDACi-ak terapia potentzial interesgarri bihurtu dira. HDACi-ek eragile neurobabesle gisa joka dezaketenez, Huntingtonen eta Parkinsonen gaixotasunetan duten eraginkortasuna aztertzen ari da. Asaldura bipolarrean eta eskizofrenian ere aurrera doa HDACi-en ikerketa.