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A Versatile High Throughput Screening System for the Simultaneous Identification of Anti-Inflammatory and Neuroprotective Compounds

Citation

Hansen, E and Krautwald, M and Maczurek, AE and Stuchbury, G and Fromm, P and Steele, M and Schulz, O and Garcia, OB and Castillo, J and Korner, H and Munch, G, 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. ISSN 1387-2877 (2010) [Refereed Article]

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Copyright Statement

Copyright © 2010 IOS Press

Official URL: http://iospress.metapress.com/content/l7714u3x87w8...

DOI: doi:10.3233/JAD-2010-1233

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-1â, 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 Details

Item Type:Refereed Article
Keywords:Co-culture, inflammation, microglia, neurons, neurotoxicity
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Korner, H (Professor Heinrich Korner)
ID Code:67831
Year Published:2010
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-03-08
Last Modified:2014-08-26
Downloads:0

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