Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse

Neurobiology of Disease
P BiginiT Mennini

Abstract

TNF-alpha overexpression may contribute to motor neuron death in amyotrophic lateral sclerosis (ALS). We investigated the intracellular pathway associated with TNF-alpha in the wobbler mouse, a murine model of ALS, at the onset of symptoms. TNF-alpha and TNFR1 overexpression and JNK/p38MAPK phosphorylation occurred in neurons and microglia in early symptomatic mice, suggesting that this activation may contribute to motor neuron damage. The involvement of TNF-alpha was further confirmed by the protective effect of treatment with rhTNF-alpha binding protein (rhTBP-1) from 4 to 9 weeks of age. rhTBP-1 reduced the progression of symptoms, motor neuron loss, gliosis and JNK/p38MAPK phosphorylation in wobbler mice, but did not reduce TNF-alpha and TNFR1 levels. rhTBP-1 might possibly bind TNF-alpha and reduce the downstream phosphorylation of two main effectors of the neuroinflammatory response, p38MAPK and JNK.

References

Dec 1, 1994·Molecular and Cellular Biology·H K SlussR J Davis
Feb 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H NawashiroJ M Hallenbeck
Feb 12, 1998·Brain Research·H NawashiroJ M Hallenbeck
Dec 16, 1998·Journal of the Neurological Sciences·J B KurekE Byrne
Jul 4, 2001·Neuroreport·P BiginiT Mennini
Feb 16, 2002·Neuroimmunomodulation·P Ghezzi, T Mennini
Apr 2, 2003·Expert Opinion on Therapeutic Targets·Sarah J Harper, Neil Wilkie
Jun 16, 2004·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·E BeghiUNKNOWN Italian Network for the Study of Motor Neuron Disease
May 10, 2005·Experimental Cell Research·Heike LiewenFrank Stenner-Liewen
Oct 26, 2005·Nature Genetics·Thomas Schmitt-JohnHarald Jockusch
Mar 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mahmoud KiaeiM Flint Beal
Jun 3, 2006·Science·Séverine BoilléeDon W Cleveland
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·David R BeersStanley H Appel

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Citations

Mar 30, 2013·Molecular Genetics and Genomics : MGG·Jakob Maximilian MoserThomas Schmitt-John
Jul 21, 2010·Cerebral Cortex·Jose Luis Nieto-GonzalezKimmo Jensen
Aug 27, 2014·BioMed Research International·Ana C CalvoRosario Osta
Aug 30, 2008·Current Opinion in Neurobiology·Georg HaaseChristopher E Henderson
Feb 26, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Maria MeyerAlejandro F De Nicola
Oct 31, 2017·Mediators of Inflammation·Massimo TortaroloCaterina Bendotti
Jan 28, 2021·International Journal of Molecular Sciences·Hilal CihankayaVeronika Matschke

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