Oxidative Stress and Epigenetic Changes in Rare Diseases

Dear Colleagues,

Research in biomedicine is currently undergoing a paradigm shift, in which the molecular bases of disease cannot be completely understood without a deep and parallel knowledge of the environmental influence on gene expression, which in turn contributes to cell differentiation and function. Epigenetic changes lie at the core of the cellular response to both external and internal stimuli which might be encrypted into the cell’s own genome, in the form of mutations and DNA alterations, but also and sometimes exclusively contained within aberrant epigenetic marks or modulators in response to external stimuli. From this perspective, oxidative stress and the impairment of the antioxidant response can guide toward alterations in the epigenetic machinery regulation that lead to the development and worsening of pathological conditions regardless of the existence of DNA alterations. Thus, a fine dissection of the epigenetic landscape underlying certain health conditions can shed light and explain particular cases of disease, adding a new layer of complexity. This approach is particularly useful in the case of rare diseases, which often appear in response not only to a certain genetic background, but also manifest with a variety of phenotypes and degrees of severity as difficult to predict as they are to treat. So-called precision medicine stands out as a promising strategy to overcome the difficulty in curing these rare diseases, which in many cases do not even correlate with genetic predisposition. Given the prominent role of oxidative stress as one of the most common symptoms accompanying cellular impairment in rare diseases, understanding the close relationship between excessive reactive species and failure of the antioxidant responses, which in turn can alter the functioning of epigenetic machinery (i.e., DNA methyltransferases and demethylases, histone acetyl transferases) and/or aberrant patterns of epigenetic modifications (i.e., histone carbonylation, nitrosylation, and sulfonylation) will undoubtedly become one of the most exciting challenges in the near future for biomedical sciences.

Dr. Carlos Romá-Mateo
Dr. José Luis García-Giménez
Dr. Pilar Gonzalez-Cabo
Guest Editors

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• redox signaling
• rare diseases
• epigenetics
• histone modifications
• noncoding RNA
• DNA methylation
• oxidative stress
• antioxidants