Repurposing Drugs via Network Analysis: Opportunities for Psychiatric Disorders

Abstract

Despite advances in pharmacology and neuroscience, the path to new medications for psychiatric disorders largely remains stagnated. Drug repurposing offers a more efficient pathway compared with de novo drug discovery with lower cost and less risk. Various computational approaches have been applied to mine the vast amount of biomedical data generated over recent decades. Among these methods, network-based drug repurposing stands out as a potent tool for the comprehension of multiple domains of knowledge considering the interactions or associations of various factors. Aligned well with the poly-pharmacology paradigm shift in drug discovery, network-based approaches offer great opportunities to discover repurposing candidates for complex psychiatric disorders. In this review, we present the potential of network-based drug repurposing in psychiatry focusing on the incentives for using network-centric repurposing, major network-based repurposing strategies and data resources, applications in psychiatry and challenges of network-based drug repurposing. This review aims to provide readers with an update on network-based drug repurposing in psychiatry. We expect the repurposing approach to become a pivotal tool in the coming years to battle debilitating psychiatric disorders.

Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine

“…Drug development typically costs 2–3 billion USD across 13–15 years from first discovery to final regulatory approval [ 107 ]. An alternative is drug repurposing, which is strongly supported by governments and funding bodies as an efficient and effective option [ 108 ] (see [ 109 ] for detailed benefits). In addition, drug repurposing may be particularly appropriate in conditions with high oxidative stress and comorbidities [ 110 , 111 ].…”

CaMKK2 as an emerging treatment target for bipolar disorder

“…An ever-expanding body of scientific literature points to the CaMKK2 signalling pathway as a contributing factor in the pathogenesis of bipolar disorder. Given the large clinical, social and economic burden of bipolar disorder, the development of better treatment options is an urgent priority; however, drug development for bipolar disorder remains virtually stagnant [ 210 ]. We propose CaMKK2 as a rational treatment target for bipolar disorder as it links together key facets of the condition including genetic polymorphisms/mutations, defects in signal transduction, mood stabiliser action, and metabolic dysfunction.…”

Human protein–protein interaction networks: A topological comparison review

“…This has resulted in the development of computational methods aimed at improving our understanding of these diseases, including identifying driver mutations in cancer [6] . Recent studies show a wide application of PPINs, such as drug repurposing [7] , [8] , [9] , disease regulation and progression [10] , virus mechanisms [11] , and multi-omics interpretation [12] .…”