Recent studies on cellular and molecular mechanisms in Alzheimer's disease: focus on epigenetic factors and histone deacetylase

Rev Neurosci. 2018 Mar 28;29(3):241-260. doi: 10.1515/revneuro-2017-0049.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders mainly affecting elderly people. It is characterized by progressive loss of memory and cognitive function. More than 95% of AD cases are related to sporadic or late-onset AD (LOAD). The etiology of LOAD is still unclear. It has been reported that environmental factors and epigenetic alterations play a significant role in AD pathogenesis. Furthermore, recently, genome-wide association studies (GWAS) identified 10 novel risk genes: ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, MS4A6A, MS4A4E, and PICALM, which play an important role for LOAD. In this review, the therapeutic approaches of AD by epigenetic modifications have been discussed. Nowadays, HDAC inhibitors have clinically proven its activity for epigenetic modifications. Furthermore, we try to establish the relationship between HDAC inhibitors and above mentioned LOAD risk genes. Finally, we are hoping that this review may open new area of research for AD treatment.

Keywords: Alzheimer’s disease; GWAS; HDAC inhibitors; LOAD; epigenetic modification.

Publication types

  • Review

MeSH terms

  • Aging / genetics
  • Aging / pathology*
  • Alzheimer Disease* / complications
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / pathology
  • Animals
  • Cognition Disorders / etiology
  • Epigenesis, Genetic / drug effects
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans

Substances

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases