Şizofrenide Güncel Translasyonel Tıp Yaklaşımı Olarak MikroRNA Araştırmaları

Öz

Şizofreni toplum sağlığını önemli ölçüde etkileyen semptomlarla seyreden yaygın ve kompleks bir psikiyatrik hastalıktır. Aday gen çalışmalarında şizofreni ile ilişkili glutamaterjik, dopaminerjik ve GABAerjik sinyal yolakları gibi moleküler yolaklarda etkin genlerde bulunan varyantların şizofreni riskini arttırdığı raporlanmıştır. Ancak, araştırmaların spesifik popülasyonlarda sınırlı sayılı örnek grupları ile sınırlı olması sebebiyle şu ana kadar elde edilen veriler translasyonel tıp alanında yeni yaklaşımların geliştirilmesi için eksik kalmaktadır. Moleküler düzeyde yapılan araştırmaların sonuçları umut verici olsa da hastalık yönetimi için gerekli erken tanı ve tedavi yöntemleri yetersizdir ve bu yönde daha fazla araştırma yapılmasına ihtiyaç duyulmaktadır. Son yıllarda yapılan çalışmalarda postmortem beyin dokusunda ve vücut sıvılarında tespit edilen bazı mikroRNA’ların şizofreni hastaları ve kontrol gruplarında farklı eksprese olarak şizofreni etiyolojisi ile ilişkili olabilecekleri raporlanmıştır. Şizofreni patofizyolojisi ile ilişkili mikroRNA profillerinin belirlenmesi hastalığın erken tanı ve tedavisinde yeni moleküler yaklaşımların geliştirilmesi açısından oldukça önemli olsa da literatürde bu alanda boşluklar vardır. Mevcut literatürde şizofreni ile ilişkili mikroRNA’ları raporlayan çalışmalar metodolojik olarak farklılıklar içermektedir. Son on yılda şizofreni ve mikroRNA ilişkisini araştıran araştırmaların incelendiği bu derleme, özellikle örnek seçiminin ve mikroRNA tespit yöntemlerinin çalışmalarda uyumlu sonuçların alınması açısından oldukça önemli olduğunu ortaya koymuştur. Postmortem beyin dokusunda eksprese olan mikroRNA’ların minimal invaziv olarak vücut sıvılarından tespiti şizofreni yönetimi için umut verici sonuçlar doğurabilir. Bu kapsamda yaptığımız kapsamlı literatür araştırması sonrası miR-124-3p, miR-16-5p ve miR-34a-5p şizofreni için potansiyel epigenetik biyobelirteç olarak önceliklendirilmiş ve mikroRNA’ların hastalığın toplumdaki yükünün hafifletilmesi için geliştirilecek translasyonel tıp yaklaşımlarında kullanım potansiyeli üzerine veri sunulmuştur.

Anahtar Kelimeler

• Şizofreni
• mikroRNA
• epigenetik
• biyobelirteç
• translasyonel tıp

Current Translational Medicine Approach in Schizophrenia: MicroRNA Research

Abstract

Schizophrenia is a common and complex psychiatric disorder with symptoms that significantly affect public health. Candidate gene studies reported that variants in genes involved in molecular processes associated with schizophrenia such as glutamatergic, dopaminergic, and GABAergic signaling pathways increase the risk of schizophrenia. Yet, the data obtained so far are incomplete for the development of new translational medicine approaches. Although the current research has promising results, it is still insufficient for the development of early diagnosis and treatment methods for schizophrenia management. Recent studies have reported that microRNAs detected in brain tissue and body fluids are differentially expressed in schizophrenia patients and control groups may be related to the etiology of schizophrenia. Although the determination of microRNA profiles associated with schizophrenia pathophysiology is very important for the development of new molecular approaches in the early diagnosis and treatment of the disease, the literature is still lacking in this field. Studies reporting schizophrenia-associated microRNAs in the existing literature have some limitations and methodological differences. In this review, we extracted the studies investigating the relationship between schizophrenia and microRNA in the last ten years and it was revealed that sample selection and microRNA detection methods are very important in terms of obtaining consistent results. Non-invasive detection of microRNAs expressed in the brain may have promising results for schizophrenia management. In this context, after a comprehensive literature search, miR-124-3p, miR-16-5p, and miR-34a-5p, which are differentially expressed in schizophrenia patients in the brain and blood, were prioritized as potential epigenetic biomarkers for schizophrenia. Our study provides data that can be utilized for translational medicine approaches to alleviate the burden of the disease in the community.

Keywords

• Schizophrenia
• microRNA
• epigenetic
• biomarker
• translational medicine

Kaynakça

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