Phenotypic screening of small-molecule inhibitors: Implications for therapeutic discovery and drug target development in traumatic brain injury

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

The inability of central nervous system (CNS) neurons to regenerate damaged axons and dendrites following traumatic brain injury (TBI) creates a substantial obstacle for functional recovery. Apoptotic cell death, deposition of scar tissue, and growth-repressive molecules produced by glia further complicate the problem and make it challenging for re-growing axons to extend across injury sites. To date, there are no approved drugs for the treatment of TBI, accentuating the need for relevant leads. Cell-based and organotypic bioassays can better mimic outcomes within the native CNS microenvironment than target-based screening methods and thus should speed the discovery of therapeutic agents that induce axon or dendrite regeneration. Additionally, when used to screen focused chemical libraries such as small-molecule protein kinase inhibitors, these assays can help elucidate molecular mechanisms involved in neurite outgrowth and regeneration as well as identify novel drug targets. Here, we describe a phenotypic cellular (high content) screening assay that utilizes brainderived primary neurons for screening small-molecule chemical libraries.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages677-688
Number of pages12
Volume1462
DOIs
StatePublished - 2016
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1462
ISSN (Print)10643745

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Keywords

  • Axon regeneration
  • Cell-based assay
  • CNS injury
  • Drug discovery
  • High-content screening
  • Kinase inhibitor
  • Primary neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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