Unlocking the concealed targets using system biology mapping for Alzheimer's disease

Alzheimer's disease (AD) constitutes a neural loss in histology of brain with involvement of complex genomic and environmental factors. Accumulation of amyloid beta (Aβ) peptide and phosphorylated tau are indicative of progression and cognitive decline. Hence an understanding of the underlying biological pathways and targets along with associated mechanisms would be useful for the development of improved therapeutics for treating AD. In the present work, we aim to identify concealed targets for developing first line therapeutics and repositioning of validated targets as well as FDA- approved drugs using a system biology approach.

We have collated information pertaining to the biological targets as well as the approved drugs, from scientific literature and patents.

In all, the imbalance in the functioning of around 79 proteins and genes were identified to be involved in Alzheimer's cascade. Amongst them, around 21 targets were found to be under therapeutic consideration for AD. Of the remaining, around 17 targets were reported as potential targets for AD, although they are under researcher's attention for other physio-pathological conditions. The analysis further revealed that ˜41 therapeutic targets are pharmacologically concealed but structurally validated targets and may constitute as potential therapeutic candidate for future drug discovery for AD.

The biological pathway vs. drug mapping provides a complete overview about underlying biological pathways, therapeutic targets (explored and concealed), associated mechanisms, existing therapeutics and the information pertaining to molecules currently under active drug development for further drug discovery and drug re-positioning/repurposing approaches for AD management.