Epigenetic Drug Repositioning for Alzheimer's Disease Based on Epigenetic Targets in Human Interactome.

BACKGROUND

Epigenetics has emerged as an important field in drug discovery. Alzheimer's disease (AD), the leading neurodegenerative disorder throughout the world, is shown to have an epigenetic basis. Currently, there are very few effective epigenetic drugs available for AD.

OBJECTIVE

In this work, for the first time we have proposed 14 AD repositioning epigenetic drugs and identified their targets from extensive human interactome.

METHODS

Interacting partners of the AD epigenetic proteins were identified from the extensive human interactome to construct Epigenetic Protein-Protein Interaction Network (EP-PPIN). Epigenetic Drug-Target Network (EP-DTN) was constructed with the drugs associated with the proteins of EP-PPIN. Regulation of non-coding RNAs associated with the target proteins of these drugs was also studied. AD related target proteins, epigenetic targets, enriched pathways, and functional categories of the proposed repositioning drugs were also studied.

RESULTS

The proposed 14 AD epigenetic repositioning drugs have overlapping targets and miRs with known AD epigenetic targets and miRs. Furthermore, several shared functional categories and enriched pathways were obtained for these drugs with FDA approved epigenetic drugs and known AD drugs.

CONCLUSIONS

The findings of our work might provide insight into future AD epigenetic-therapeutics.