Article

Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.

Institute of Neuroimmunology, Neuroscience Research Center, Charité, University-Medicine, NWFZ 2680, Charité, 10098 Berlin, Germany.
Journal of Neuroimmunology (impact factor: 2.96). 11/2005; 167(1-2):204-9. DOI:10.1016/j.jneuroim.2005.06.027 pp.204-9
Source: PubMed

ABSTRACT Neuronal damage mediated by the TRAIL-system might be involved in the pathogenesis of neuroinflammatory diseases of the central nervous system. Here we used an investigator-independent approach to quantify TRAIL-mediated death of total CNS cells and neurons in a living human brain slice culture system, a model which is much closer to the in vivo situation than dissociated cell culture. We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties. Our data suggest flupirtine-maleate as an orally available neuroprotective approach in the course of neuroinflammation.

0 0
 · 
0 Bookmarks
 · 
26 Views
  • Source
    Article: The Biology of TRAIL and the Role of TRAIL-Based Therapeutics in Infectious Diseases.
    Brett D Shepard, Andrew D Badley
    [show abstract] [hide abstract]
    ABSTRACT: TNF-related apoptosis inducing ligand (TRAIL) is a key mediator of the innate immune response to infection. While TRAIL-mediated apoptosis plays an essential role in the clearance of virus-infected cells, its physiologic role also includes immunosurveilance for cancer cells. Therapeutics that induce TRAIL-mediated apoptosis in cancer cells remain a focus of ongoing investigation in clinical trials, and much has been learned from these studies regarding the efficacy and toxicity of these interventions. These data, combined with data from numerous preclinical studies that detail the important and multifaceted role of TRAIL during infection with human immunodeficiency virus and other viruses, suggest that therapeutic exploitation of TRAIL signaling offers a novel and efficacious strategy for the management of infectious diseases.
    Anti-infective agents in medicinal chemistry. 04/2009; 8(2):87-101.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

analgesic drug
 
dissociated cell culture
 
dose-dependent TRAIL-mediated death
 
flupirtine-maleate
 
living human brain slice culture system
 
neuroinflammation
 
neuroinflammatory diseases
 
neurons
 
total CNS cells
 
total human CNS cells
 
TRAIL-mediated death