Inhibition of microglia activation as a phenotypic assay in early drug discovery

Mariana Figuera-Losada, Camilo Rojas, Barbara S. Slusher

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Complex biological processes such as inflammation, cell death, migration, proliferation, and the release of biologically active molecules can be used as outcomes in phenotypic assays during early stages of drug discovery. Although target-based approaches have been widely used over the past decades, a disproportionate number of first-in-class drugs have been identified using phenotypic screening. This review details phenotypic assays based on inhibition of microglial activation and their utility in primary and secondary screening, target validation, and pathway elucidation. The role of microglia, both in normal as well as in pathological conditions such as chronic neurodegenerative diseases, is reviewed. Methodologies to assess microglia activation in vitro are discussed in detail, and classes of therapeutic drugs known to decrease the proinflammatory and cytotoxic responses of activated microglia are appraised, including inhibitors of glutaminase, cystine/glutamate antiporter, nuclear factor κB, and mitogen-activated protein kinases.

Original languageEnglish (US)
Pages (from-to)17-31
Number of pages15
JournalJournal of Biomolecular Screening
Volume19
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Fingerprint

Microglia
Drug Discovery
Assays
Chemical activation
Screening
Neurodegenerative diseases
Glutaminase
Antiporters
Biological Phenomena
Cystine
Cell death
Mitogen-Activated Protein Kinases
Neurodegenerative Diseases
Pharmaceutical Preparations
Cell Movement
Glutamic Acid
Chronic Disease
Cell Death
Inflammation
Molecules

Keywords

  • cell-based assays
  • cytokines
  • glutamate
  • nitric oxide
  • reactive oxygen species
  • screening

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

Cite this

Inhibition of microglia activation as a phenotypic assay in early drug discovery. / Figuera-Losada, Mariana; Rojas, Camilo; Slusher, Barbara S.

In: Journal of Biomolecular Screening, Vol. 19, No. 1, 01.2014, p. 17-31.

Research output: Contribution to journalArticle

Figuera-Losada, Mariana ; Rojas, Camilo ; Slusher, Barbara S. / Inhibition of microglia activation as a phenotypic assay in early drug discovery. In: Journal of Biomolecular Screening. 2014 ; Vol. 19, No. 1. pp. 17-31.
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