Pharmacoepigenomic Interventions as Novel Potential Treatments for Alzheimer's and Parkinson's Diseases

Int J Mol Sci. 2018 Oct 16;19(10):3199. doi: 10.3390/ijms19103199.

Abstract

Cerebrovascular and neurodegenerative disorders affect one billion people around the world and result from a combination of genomic, epigenomic, metabolic, and environmental factors. Diagnosis at late stages of disease progression, limited knowledge of gene biomarkers and molecular mechanisms of the pathology, and conventional compounds based on symptomatic rather than mechanistic features, determine the lack of success of current treatments, including current FDA-approved conventional drugs. The epigenetic approach opens new avenues for the detection of early presymptomatic pathological events that would allow the implementation of novel strategies in order to stop or delay the pathological process. The reversibility and potential restoring of epigenetic aberrations along with their potential use as targets for pharmacological and dietary interventions sited the use of epidrugs as potential novel candidates for successful treatments of multifactorial disorders involving neurodegeneration. This manuscript includes a description of the most relevant epigenetic mechanisms involved in the most prevalent neurodegenerative disorders worldwide, as well as the main potential epigenetic-based compounds under investigation for treatment of those disorders and their limitations.

Keywords: Alzheimer’s disease (AD), DNA methyltransferase inhibitors/activators; Histone deacetylase inhibitors; Parkinson’s disease (PD), sirtuin activators; histone acetyltransferase activators/inhibitors; histone demethylase inhibitors; histone methyltransferase inhibitors; non-coding RNAs.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / therapy*
  • Epigenomics*
  • Humans
  • Molecular Targeted Therapy
  • Nerve Degeneration / genetics
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Pharmacogenetics*