DNA methylation in amyotrophic lateral sclerosis: where do we stand and what is next?

Genes involved in immune response, inflammation and metabolism are among those most likely affected by changes in DNA methylation (DNAm) and expression levels in amyotrophic lateral sclerosis (ALS) tissues. Unfortunately, it is still largely unclear whether any of these changes precede the onset of disease symptoms or whether most of them are the result of the muscular and metabolic changes that follow symptoms onset. In this article the author discusses the strengths and limitations of the available studies of DNAm in ALS and provides some suggestions on what, in his opinion, could be done in the near future for a better understanding of the DNAm changes occurring in ALS, their link with environmental exposures and their potential clinical utility.