Epigenetic cerebellar diseases.

Epigenetics is a growing field of knowledge that is changing our understanding of pathologic processes. For many cerebellar disorders, recent discoveries of epigenetic mechanisms help us to understand their pathophysiology. In this chapter, a short explanation of each epigenetic mechanism (including methylation, histone modification, and miRNA) is followed by references to those cerebellar disorders in which relevant epigenetic advances have been made. The importance of normal timing and distribution of methylation during neurodevelopment is explained. Abnormal methylation and altered gene expression in the developing cerebellum have been related to neurodevelopmental disorders such as autism, Rett syndrome, and fragile X syndrome. DNA packaging by histones is another important epigenetic mechanism in cerebellar functioning. Current knowledge of histone abnormalities in cerebellar diseases such as Friedreich ataxia and spinocerebellar ataxias is reviewed, including implications for new therapeutic approaches to these degenerative diseases. Finally, micro RNAs, the third mechanism to modulate DNA expression, and their role in normal cerebellar development and disease are described. Understanding how genetic and epigenetic mechanisms interact not only in normal cerebellar development but also in disease is a great challenge. However, such understanding will lead to promising new therapeutic possibilities as is already occurring in other areas of medicine.