Role of 5-hydroxymethylcytosine in neurodegeneration

The recent discovery of 5-hydroxymethylcytosine (5hmC), an epigenetic modifier and oxidation product of 5-methylcytosine (5mC), has broadened the scope and understanding of neural development and neurodegenerative diseases. By virtue of their functional groups, 5mC and 5hmC exert opposite effects on gene expression; the former is generally associated with gene silencing whereas the latter is mainly involved in up-regulation of gene expression affecting the cellular processes such as differentiation, development, and aging. Although DNA methylation plays an important role in normal neural development and neuroprotection, an altered pathway due to complex interaction with environmental and genetic factors may cause severe neurodegeneration. The levels of 5hmC in brain increase progressively from birth until death, while in patients with neurodegenerative disorders, the levels are found to be highly compromised. This article discusses the recent developments in the area of hydroxymethylation, with particular emphasis on the role of 5hmC in neurodegenerative diseases including Alzheimer's disease, Parkinson's diseases and Huntington's disease. We have also included recent findings on the role of 5hmC in brain tumors (gliomas). Despite compelling evidence on the involvement of 5hmC in neurodegeneration, it is yet to be established whether this epigenetic molecule is the cause or the effect of the onset and progression of neurodegenerative diseases.