Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.

Journal Article (Journal Article)

Disrupted cellular trafficking and transport processes are hallmarks of many neurodegenerative disorders (NDs). Recently, efforts have been made toward developing and implementing experimental platforms to identify small molecules that may help restore normative trafficking functions. There have been a number of successes in targeting endomembrane trafficking with the identification of compounds that restore cell viability through rescue of protein transport and trafficking. Here, we describe some of the experimental platforms implemented for small molecule screening efforts for rescue of trafficking defects in neurodegeneration. A survey of phenotypically active small molecules identified to date is provided, including a summary of medicinal chemistry efforts and insights into putative targets and mechanisms of action. In particular, emphasis is put on ligands that demonstrate activity in more than one model of neurodegeneration as retention of phenotypic activity across ND models suggests conservation of biological targets across NDs.

Full Text

Duke Authors

Cited Authors

  • Hatstat, AK; Pupi, MD; Reinhart, MC; McCafferty, DG

Published Date

  • November 2021

Published In

Volume / Issue

  • 12 / 21

Start / End Page

  • 3972 - 3984

PubMed ID

  • 34652126

Electronic International Standard Serial Number (EISSN)

  • 1948-7193

International Standard Serial Number (ISSN)

  • 1948-7193

Digital Object Identifier (DOI)

  • 10.1021/acschemneuro.1c00524


  • eng