1. Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse
- Author
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Rossella Tonelli, Mariaelena Repici, Renato Bernardini, Paolo Bigini, Alfredo Cagnotto, Giuseppina Cantarella, Tiziana Mennini, Ada De Luigi, Tiziana Borsello, Elena Fumagalli, and Sara Barbera
- Subjects
Male ,Cell Count ,lcsh:RC321-571 ,Mice ,Mice, Neurologic Mutants ,medicine ,Animals ,Humans ,Amyotrophic lateral sclerosis ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Motor Neurons ,Microglia ,Tumor Necrosis Factor-alpha ,business.industry ,Binding protein ,Amyotrophic Lateral Sclerosis ,rhTBP-1 ,Motor neuron ,medicine.disease ,Recombinant Proteins ,TNFR1 ,Tumor Necrosis Factor Decoy Receptors ,medicine.anatomical_structure ,Neurology ,Gliosis ,Receptors, Tumor Necrosis Factor, Type I ,Motor neuron degeneration ,Wobbler ,Immunology ,Disease Progression ,p38MAPK ,Cancer research ,Phosphorylation ,Female ,Tumor necrosis factor alpha ,JNK ,medicine.symptom ,business ,Intracellular - 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.
- Published
- 2008