The impact of histone post-translational modifications in neurodegenerative diseases

Highlights

• Cures for neurodegenerative disorders have yet to be discovered

• Classical genetics fails to outline the pathology of neurodegenerative diseases

• Histone PTMs and other epigenetic mechanisms may hold important clues to understanding neurodegenerative disease.

• Agents targeting epigenetic systems offer a promising approach for neurodegenerative disease treatment.

Abstract

Every year, neurodegenerative disorders take more than 5000 lives in the US alone. Cures have not yet been found for many of the multitude of neuropathies. The majority of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) cases have no known genetic basis. Thus, it is evident that contemporary genetic approaches have failed to explain the etiology or etiologies of ALS/FTD and PD. Recent investigations have explored the potential role of epigenetic mechanisms in disease development. Epigenetics comprises heritable changes in gene utilization that are not derived from changes in the genome. A main epigenetic mechanism involves the post-translational modification of histones. Increased knowledge of the epigenomic landscape of neurodegenerative diseases would not only further our understanding of the disease pathologies, but also lead to the development of treatments able to halt their progress. Here, we review recent advances on the association of histone post-translational modifications with ALS, FTD, PD and several ataxias.