The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons.
In NFL-/- mice, a model of motor neuron degeneration in ALS, degenerating spinal motor neurons express high levels of the receptor for the C5a anaphylatoxin (C5aR) early in the disease process. C5a is a potent in vitro neurotoxin for both Neuro2A and NGF-differentiated PC12 cells. While no interaction was observed between glutamate and C5a, both C5a and kainate upregulated the expression of activated C5aR. C5aR expression was increased in motor neurons in ALS. This data suggests that the early upregulation of C5aR may contribute to motor neuron damage that potentiates excitotoxicity in ALS.
Humayun
Saima
S
Department of Pathology, Schulich School of Medicine, University of Western Ontario, London, Canada.
Gohar
May
M
Volkening
Kathryn
K
Moisse
Katie
K
Leystra-Lantz
Cheryl
C
Mepham
Jennifer
J
McLean
Jesse
J
Strong
Michael J
MJ
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015936:Complement C5a / Q000494:pharmacology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016472:Motor Neuron Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics*; D009498:Neurotoxins / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D018690:Excitatory Amino Acid Agonists; D016900:Neurofilament Proteins; D009498:Neurotoxins; D044087:Receptor, Anaphylatoxin C5a; C044882:neurofilament protein L; D015936:Complement C5a; D007608:Kainic Acid