Translational Informatics Driven Drug Repositioning for Neurodegenerative Disease

Abstract: Neurodegenerative diseases represent a prevalent category of age-associated diseases. As human lifespans extend and societies become increasingly aged, neurodegenerative diseases pose a growing threat to public health. The lack of effective therapeutic drugs for both common and rare neurodegenerative diseases amplifies the medical challenges they present. Current treatments for these diseases primarily offer symptomatic relief rather than a cure, underscoring the pressing need to develop efficacious therapeutic interventions. Drug repositioning, an innovative and data-driven approach to research and development, proposes the re-evaluation of existing drugs for potential application in new therapeutic areas. Fueled by rapid advancements in artificial intelligence and the burgeoning accumulation of medical data, drug repositioning has emerged as a promising pathway for drug discovery. This review comprehensively examines drug repositioning for neurodegenerative diseases through the lens of translational informatics, encompassing data sources, computational models, and clinical applications. Initially, we systematized drug repositioning-related databases and online platforms, focusing on data resource management and standardization. Subsequently, we classify computational models for drug repositioning from the perspectives of drug-drug, drug-target, and drug-disease interactions into categories such as machine learning, deep learning, and networkbased approaches. Lastly, we highlight computational models presently utilized in neurodegenerative disease research and identify databases that hold potential for future drug repositioning efforts. In the artificial intelligence era, drug repositioning, as a data-driven strategy, offers a promising avenue for developing treatments suited to the complex and multifaceted nature of neurodegenerative diseases. These advancements could furnish patients with more rapid, cost-effective therapeutic options.