Epigenetic Regulation of ALS and CMT: A Lesson fromModels.

Abstract

Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disorder and is sometimes associated with frontotemporal dementia. Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited peripheral neuropathies causing the slow progression of sensory and distal muscle defects. Of note, the severity and progression of CMT symptoms markedly vary. The phenotypic heterogeneity of ALS and CMT suggests the existence of modifiers that determine disease characteristics. Epigenetic regulation of biological functions via gene expression without alterations in the DNA sequence may be an important factor. The methylation of DNA, noncoding RNA, and post-translational modification of histones are the major epigenetic mechanisms. Currently,is emerging as a useful ALS and CMT model. In this review, we summarize recent studies linking ALS and CMT to epigenetic regulation with a strong emphasis on approaches usingmodels.