Histone Modifications in Alzheimer's Disease

Genes (Basel). 2023 Jan 29;14(2):347. doi: 10.3390/genes14020347.

Abstract

Since Late-onset Alzheimer's disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease's onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer's disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.

Keywords: Alzheimer’s disease; aging; histone modifications.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • DNA Methylation
  • Epigenesis, Genetic
  • Histone Code
  • Histone Deacetylase Inhibitors / pharmacology
  • Histones / genetics
  • Humans

Substances

  • Histones
  • Histone Deacetylase Inhibitors

Grants and funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: Finance Code: 001; Fundação de Amparo à Pesquisa do Estado de São Paulo: Auxílio à pesquisa: processo nº 2016/25562-0; Conselho Nacional de Desenvolvimento Científico e Tecnológico: Auxílio à pesquisa—Edital Doenças Neurodegenerativas: processo nº 406966/2016-8.