INTRINSIC MECHANISM OF ANTICANCER DRUGS IN NEURODEGENERATIVE DISORDERS

Abstract

As the global population is growing progressively older, the prevalence of life-threatening neurodegenerative disorders is increasing. The mechanism and pathologies of these disorders are still undecipherable and only disease-modifying treatments are available. Drug therapy is crucial for treating serious neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. The immediate need for exploring novel treatment options calls for designing efficacious drug development strategies. In the recent past, there has been a growing interest in drug repurposing for incurable diseases. Drug repurposing offers an accelerated pathway for using existing drugs for novel indications with remarkable reduction in drug development time and cost. Advancements in screening technologies and the discovery of data-driven repurposing strategies have expedited the repurposing process for various diseases. In the context of neurodegenerative disorders, anticancer drugs are gaining immense attention and various drugs have been tested in different neurodegenerative disorders. Currently, various computational methods, including molecular, structural and clinical methods, present great opportunities to investigate repurposed drugs for neurodegenerative disorders. However, the heterogeneous disease states, lack of effective validation methods and experimental obstacles oppose the process of drug development. Therefore, we identified the problem of lack of efficacious methods to facilitate drug repurposing for various neurodegenerative disorders, specifically Alzheimer's disease and Parkinson's disease. Here, the main objective of this Ph.D. work is to understand the biological rationale for repurposing anticancer drugs for neurodegenerative disorders. We investigated the common molecular mechanism of Alzheimer's disease, Parkinson's disease and cancer. We opted an integrated approach including genomics, transcriptomics and proteomics data to unravel the ix | P a g e common molecular signatures. Further, we extensively analyzed the overlapping pathways, biological processes and regulatory signatures such as transcription factors and micro RNAs. We explored various FDA-approved anticancer drugs and validated their repurposing potential as neuroprotectants by applying different computational methods such as structural similarities, Cmap analysis, molecular docking and simulations. To further extend our research, we also explored the repurposing aspects of natural anticancer compounds for some common targets against Alzheimer's and Parkinson's diseases.