Publication:

Interrogating the epigenome to unveil the secrets of neurodegeneration: promising epigenetic therapies

According to the WHO, cerebrovascular and neurodegenerative disorders affect one billion people around the world. Pathological phenotypes of neurodegeneration result from a combination of genomic, epigenomic, metabolic, and environmental factors, which hinder their treatment. Indeed, current FDA-approved conventional drugs used for treatment of neurodegenerative disorders provide very little beneficial effects, or, at best, reduce the pathological symptoms but do not detain disease progression. Furthermore, the unacceptable side effects of most of these treatments make them unsuitable for chronic treatments. One of the main reasons for this historical setback correlates with the poor knowledge about the molecular mechanisms of these pathologies, which results in the inappropriate drug target selection. Genetic components did not fully explain the mechanisms of those diseases. Furthermore, most treatments target symptomatic features of disease but they are not antipathogenic. During the last 15 years, the study of the role of the epigenetic machinery on gene regulation opens new and promising perspectives for a more accurate and effective treatment. Aberrant alterations in the epigenetic machinery result in dysregulation of gene expression at different levels in pathological conditions compared to healthy controls. The epigenetic approach allows the identification of key pathological targets in complex disorders that cannot be detected using genetic-based methods. Many of these epigenetic targets may be detected in early asymptomatic stages of the disease, which facilitates its treatment. Furthermore, the reversibility and potential restoring of epigenetic aberrations, unlike genetic mutations, sited epigenetic-based therapy as a promising tool to treat those complex disorders. This manuscript reviews the main epigenetic mechanisms involved in the most relevant neurodegenerative disorders nowadays, as well as the potential epigenetic-based drugs currently used in clinical trials for treatment of those disorders and future perspectives.