EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, 15165 La Coruña, Spain.
Chair of Genomic Medicine, Continental University Medical School, Huancayo 12000, Peru.
Int J Mol Sci. 2018 Oct 16;19(10):3199. doi: 10.3390/ijms19103199.
Cerebrovascular and neurodegenerative disorders affect one billion people around the world and result from a combination of genomic, epigenomic, metabolic, and environmental factors. Diagnosis at late stages of disease progression, limited knowledge of gene biomarkers and molecular mechanisms of the pathology, and conventional compounds based on symptomatic rather than mechanistic features, determine the lack of success of current treatments, including current FDA-approved conventional drugs. The epigenetic approach opens new avenues for the detection of early presymptomatic pathological events that would allow the implementation of novel strategies in order to stop or delay the pathological process. The reversibility and potential restoring of epigenetic aberrations along with their potential use as targets for pharmacological and dietary interventions sited the use of epidrugs as potential novel candidates for successful treatments of multifactorial disorders involving neurodegeneration. This manuscript includes a description of the most relevant epigenetic mechanisms involved in the most prevalent neurodegenerative disorders worldwide, as well as the main potential epigenetic-based compounds under investigation for treatment of those disorders and their limitations.
脑血管和神经退行性疾病影响着全球十亿人口，是由基因组、表观基因组、代谢和环境因素共同作用的结果。疾病进展后期的诊断、对基因生物标志物和病理分子机制的有限了解，以及基于症状而非机制特征的传统化合物，决定了目前治疗方法的失败，包括目前 FDA 批准的传统药物。表观遗传学方法为检测早期无症状病理事件开辟了新途径，这将允许实施新策略以阻止或延缓病理过程。表观遗传改变的可逆性和潜在恢复，以及将其作为药理学和饮食干预靶点的潜力，使表药物成为成功治疗涉及神经退行性变的多因素疾病的潜在新型候选药物。本文描述了与全球最常见的神经退行性疾病相关的最相关的表观遗传机制，以及正在研究用于治疗这些疾病的主要潜在基于表观遗传的化合物及其局限性。
