Bioactive Compound Screen for Pharmacological Enhancers of Apolipoprotein E in Primary Human Astrocytes

Gina M. Finan, Ronald Realubit, Sungkwon Chung, Dieter Lütjohann, Nan Wang, John R. Cirrito, Charles Karan, Tae Wan Kim

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Pharmacological screening in physiologically relevant brain cells is crucial for identifying neuroactive compounds that better translate into in vivo biology and efficacious therapeutics. Pharmacological enhancement of apolipoprotein E (apoE), a cholesterol-transporting apolipoprotein, has been proposed as a promising therapeutic approach for Alzheimer's disease. Several nuclear receptor agonists were initially shown to increase brain apoE levels together with ATP-binding cassette transporter 1 (ABCA1), but their underlying mechanisms remain unclear. To gain an insight on brain apoE regulation, we performed an unbiased high-throughput screening of known drugs and bioactive compounds in cultured human primary astrocytes, the major apoE-producing cell type in the brain. We have identified several small molecules that increase apoE secretion via previously unknown mechanisms, including those not co-inducing ABCA1. These newly identified compounds are active preferentially in human astrocytes but not in an astrocytoma cell line, furnishing new tools for investigating biological pathways underlying brain apoE production.

Original languageEnglish
Pages (from-to)1526-1538
Number of pages13
JournalCell Chemical Biology
Issue number12
StatePublished - Dec 22 2016


  • Alzheimer's disease
  • apolipoprotein E (apoE)
  • astrocyte
  • chemical biology
  • cholesterol
  • drug discovery
  • high-throughput screening (HTS)
  • phenotypic screening
  • primary cells


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