A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds

Elizabeth Hansen, Martina Krautwald, Annette E. Maczurek, Grant Stuchbury, Phillip Fromm, Megan Steele, Oliver Schulz, Obdulio Benavente Garcia, Julian Castillo, Heinrich Korner, Gerald Münch

    Research output: Contribution to journalArticlepeer-review

    25 Citations (Scopus)

    Abstract

    In many chronic neurodegenerative diseases including Frontotemporal Dementia and Alzheimer's disease (AD), microglial activation is suggested to be involved in pathogenesis or disease progression. Activated microglia secrete a variety of cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor as well as reactive oxygen and nitrogen species (ROS/RNS). ROS and RNS contribute to alterations in neuronal glucose uptake, inhibition of mitochondrial enzymes, a decrease in mitochondrial membrane potential, impaired axonal transport, and synaptic signaling. In addition, ROS act as signaling molecules in pro-inflammatory redox-active signal transduction pathways. To establish a high throughput screening system for anti-inflammatory and neuroprotective compounds, we have constructed an "Enhanced Green Fluorescent protein" (EGFP) expressing neuronal cell line and set up a murine microglia/neuron co-culture system with these EGFP expressing neuronal cells. We show that microglia activation leads to neuronal cell death, which can be conveniently measured by loss of neuronal EGFP fluorescence. Moreover, we used this system to test selected polyphenolic compounds for their ability to downregulate inflammatory markers and to protect neurons against microglial insult. We suggest that this system might allow accelerated drug discovery for the treatment of inflammation-mediated neurodegenerative diseases.
    Original languageEnglish
    Pages (from-to)437-450
    Number of pages14
    JournalJournal of Alzheimer's Disease
    Volume19
    Issue number2
    DOIs
    Publication statusPublished - 2010

    Fingerprint

    Dive into the research topics of 'A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds'. Together they form a unique fingerprint.

    Cite this