NR AQIE
AU Burwinkel,M.; Schwarz,A.; Riemer,C.; Schultz,J.; van Landeghem,F.; Baier,M.
TI Rapid disease development in scrapie-infected mice deficient for CD40 ligand
QU EMBO Reports 2004 May; 5(5): 527-31
IA http://www.nature.com/embor/journal/v5/n5/pdf/7400125.pdf
PT journal article
AB The inhibition of CD40-CD40L interaction-mediated signalling was suggested as a therapeutic strategy for the treatment of Alzheimer's disease. Conversely, CD40-deficient neurons were reported to be more vulnerable to stress associated with ageing as well as nerve growth factor-beta and serum withdrawal. We studied the scrapie infection of CD40L-deficient (CD40L(-/-)) mice to see whether ablation of the CD40L gene would be beneficial or detrimental in this model of a neurodegenerative amyloidosis. CD40L(-/-) mice died on average 40 days earlier than wild-type control mice and exhibited a more pronounced vacuolation of the neuropil and an increased microglia activation. The experimental model indicates that a deficiency for CD40L is highly detrimental in prion diseases and reinforces the neuroprotective function of intact CD40-CD40L interactions. The stimulation of neuroprotective pathways may represent a possibility to delay therapeutically the disease onset in prion infections of the central nervous system.
MH Alzheimer Disease/physiopathology; Animals; Antigens, CD40/metabolism; Biological Markers; Brain/cytology/metabolism/pathology; CD40 Ligand/genetics/*metabolism; Disease Progression; Female; Humans; Mice; Mice, Inbred Strains; Mice, Knockout; *Neurons/cytology/metabolism/pathology; Prions/metabolism; Research Support, Non-U.S. Gov't; *Scrapie/genetics/metabolism/pathology; Signal Transduction/physiology; Survival Rate; gamma-Aminobutyric Acid/metabolism
AD Project 'Neurodegenerative Diseases', Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
SP englisch
PO England