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Identification of Potentially Repurposable Drugs for Lewy Body Dementia Using a Network-Based Approach.

Megha Manoj1, Siddarth Sowmyanarayan1, Arjun V Kowshik1

  • 1Department of Biotechnology, PES University, Bangalore, 560085, India.

Journal of Molecular Neuroscience : MN
|February 16, 2024
PubMed
Summary
This summary is machine-generated.

This study repurposed existing drugs for Lewy body dementia (LBD) using network medicine. Researchers identified 8 antidepressant drugs, including selective serotonin and norepinephrine inhibitors, as potential treatments for LBD.

Keywords:
AntidepressantInteractomeLewy body dementiaNetwork medicineSynaptic vesicle pathway

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Computational Biology

Background:

  • Lewy body dementia (LBD) is a progressive neurological disorder with no effective cure, characterized by neuronal loss and diverse symptoms.
  • Conventional single-target drug approaches have failed to provide therapeutic solutions for LBD.

Purpose of the Study:

  • To repurpose existing drugs for treating Lewy body dementia (LBD) by employing a network medicine approach.
  • To identify potential therapeutic candidates by analyzing drug interactions with disease-related genes and proteins.

Main Methods:

  • Utilized the SAveRUNNER algorithm to assess drug proximity to LBD-associated genes and protein targets within the human interactome.
  • Employed Connectivity Map (CMap) for gene set enrichment analysis and EnrichR for pathway enrichment analysis to validate drug candidates.
  • Focused on the synaptic vesicle pathway identified as significant in LBD pathogenesis.

Main Results:

  • Predicted 154 FDA-approved drugs, many targeting nervous system disorders, with quinapril and selegiline noted for off-label potential.
  • Identified 8 antidepressant drugs, targeting serotonin, dopamine, and norepinephrine transporters, as promising candidates for LBD treatment.
  • Validated selective serotonin and norepinephrine reuptake inhibitors (SSRIs/SNRIs) like milnacipran, protriptyline, and venlafaxine for potential LBD management.

Conclusions:

  • Network medicine and drug repurposing offer a viable strategy for identifying novel LBD therapeutics.
  • Specific antidepressant drugs targeting monoamine transporters show promise in managing LBD and its associated symptoms.
  • Further investigation into these identified drug candidates could lead to effective LBD treatments.