Epigenetics in neurological disease

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About this Research Topic

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Background

Neurological diseases cause significant pressures for affected individuals and their families, with serious medical, social, emotional and financial costs associated with managing these diseases and caring for those in need. These include monogenetic and complex diseases, such as Huntington disease, Parkinson disease, cancers and mental illnesses, affecting the central and peripheral nervous systems. The molecular mechanisms underlying the pathology of neurological diseases are diverse, ranging from aberrant gene silencing or overexpression through to production of toxic RNAs and/or proteins.

The importance of epigenetic regulation in neurological functions and disease, and its potential influence on clinical parameters, is only now being realized. Accumulating evidence implicates aberrant DNA methylation, histone modifications and chromatin remodeling in disease etiology. Epigenetic profiling in neurological disease is challenging since disease varies significantly in progression, severity and penetrance, and neurological tissues cannot be easily accessed. It is therefore important to develop a wide range of informative cellular models, animal models and xenograft models of neurological disease for use in epigenetics research and biomarker evaluation. Evaluating readily accessible human tissues, such as blood, is also important for use in ongoing treatment monitoring and the development of prognostic biomarkers.

Understanding the interactions between the epigenetic profile, genetic predisposition, environmental risk and other pathological mechanisms could provide insight into disease mechanism and facilitate the development of new treatments and biomarkers in a more targeted way. It could also lead to the identification of previously unknown therapeutic targets. The effectiveness of epigenetic-based therapies will depend on the pathogenic mechanism and mode of action. Established epigenetic modifiers such as HDAC inhibitors are currently in trial for multiple neurological diseases, with several more in the experimental phase. Others in development include pharmacological agents that mediate DNA demethylation, histone modification, and anti-sense oligonucleotides and small RNAs. Ultimately, it is likely that a combination of therapies will be needed.

We welcome the submission of papers presenting and discussing the latest advances and current challenges in the field of epigenetics in neurological disease. Highlighting critical unresolved issues and future directions is essential. Topics of interest include, but are not limited to:
• Epigenetic studies using cellular and animal models of neurological disease
• Characterizing the epigenetic mechanisms and factors involved in neurological disease pathology
• Evaluating the associations between genetic, epigenetic and clinical parameters of neurological disease
• Systems biology studies that incorporate analyses of the epigenome in neurological disease
• Identifying epigenetic biomarkers for neurological disease in a variety of tissues (e.g. blood, skin, muscle, brain)
• Studies examining the impact of epigenetics on clinical outcome in neurological disease

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