A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds
Hansen, Elizabeth, Krautwald, Martina, Maczurek, Annette E., Stuchbury, Grant, Fromm, Phillip, Steele, Megan, Schulz, Oliver, Garcia, Obdulio Benavente, Castillo, Julian, Körner, Heinrich, and Münch, Gerald (2010) A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds. Journal of Alzheimer's Disease, 19 (2). pp. 451-464.
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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.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||co-culture, inflammation, microglia, neurons, neurotoxicity|
|Date Deposited:||30 May 2011 07:07|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110199 Medical Biochemistry and Metabolomics not elsewhere classified @ 100%|
|SEO Codes:||92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%|
|Citation Count from Web of Science||