Advances in the Genetics and Epigenetics of Neurodegenerative Diseases

Abstract

AbstractAlzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) represent four of the major neurodegenerative diseases. AD, PD and ALS are complex disorders including both Mendelian and sporadic forms. Studies on families with these diseases led to the identification of several genes and pathways responsible for the familial forms. Those studies have been paralleled by hundreds of genetic association studies, including genome-wide screenings, in order to identify genes likely contributing to the sporadic forms. HD is a monogenic disorder caused by a trinucleotide repeat expansion in the causative gene. Increasing evidence points to an epigenetic contribution to neurodegeneration, suggesting that DNA methylation, histone tail modifications and RNA mediated mechanisms might contribute to the onset and progression of all the above diseases. In addition, epigenetic drugs are promising for the restoration of memory and motor impairments in animal models of the diseases. The aim of this review article is to provide an updated overview of the genetics and epigenetics of these major neurodegenerative disorders.