Epigenetics in neurodegeneration: a new layer of complexity

Several diseases are known to have a multifactorial origin, depending not only on genetic but also on environmental factors. They are called "complex disorders" and include cardiovascular disease, cancer, diabetes, and neuropsychiatric and neurodegenerative diseases. In the latter class, Alzheimer's (AD) and Parkinson's diseases (PD) are by far the most common in the elderly and constitute a tremendous social and economical problem. Both disorders present familial and sporadic forms and although some polymorphisms and risk factors have been associated with AD and PD, the precise way by which the environment contributes to neurodegeneration is still unclear. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, and chromatin remodeling, which may induce alterations in gene expression programs. Epigenetics, which refers to any process that alters gene activity without changing the actual DNA sequence, and leads to modifications that can be transmitted to daughter cells, is a relatively novel area of research that is currently attracting a high level of interest. Epigenetic modulation is present since the prenatal stages, and the aging process is now accepted to be associated with a loss of phenotypic plasticity to epigenetic modifications. Since aging is the most important risk factor for idiopathic AD and PD, it is expected that epigenetic alterations on DNA and/or chromatin structure may also accumulate in neurodegeneration, accounting at least in part to the etiology of these disorders.