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

Paolo Bigini; Mariaelena Repici; Giuseppina Cantarella; Elena Fumagalli; Sara Barbera; Alfredo Cagnotto; Ada De Luigi; Rossella Tonelli; Renato Bernardini; Tiziana Borsello; Tiziana Mennini

doi:10.1016/j.nbd.2007.11.005

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

Paolo Bigini, Mariaelena Repici, Giuseppina Cantarella, Elena Fumagalli, Sara Barbera, Alfredo Cagnotto, Ada De Luigi, Rossella Tonelli, Renato Bernardini, Tiziana Borsello, Tiziana Mennini

College of Health and Life Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	465-476
Number of pages	12
Journal	Neurobiology of Disease
Volume	29
Issue number	3
DOIs	https://doi.org/10.1016/j.nbd.2007.11.005
Publication status	Published - Mar 2008

Keywords

Amyotrophic Lateral Sclerosis/genetics
Animals
Cell Count/methods
Disease Progression
Female
Humans
Male
Mice
Mice, Neurologic Mutants
Motor Neurons/drug effects
Receptors, Tumor Necrosis Factor, Type I/administration & dosage
Recombinant Proteins/administration & dosage
Tumor Necrosis Factor Decoy Receptors/administration & dosage
Tumor Necrosis Factor-alpha/antagonists & inhibitors

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10.1016/j.nbd.2007.11.005

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Bigini, P., Repici, M., Cantarella, G., Fumagalli, E., Barbera, S., Cagnotto, A., De Luigi, A., Tonelli, R., Bernardini, R., Borsello, T., & Mennini, T. (2008). Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse. Neurobiology of Disease, 29(3), 465-476. https://doi.org/10.1016/j.nbd.2007.11.005

@article{f733c588357b4c5aa61b6539a3e5970b,

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

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.",

keywords = "Amyotrophic Lateral Sclerosis/genetics, Animals, Cell Count/methods, Disease Progression, Female, Humans, Male, Mice, Mice, Neurologic Mutants, Motor Neurons/drug effects, Receptors, Tumor Necrosis Factor, Type I/administration & dosage, Recombinant Proteins/administration & dosage, Tumor Necrosis Factor Decoy Receptors/administration & dosage, Tumor Necrosis Factor-alpha/antagonists & inhibitors",

author = "Paolo Bigini and Mariaelena Repici and Giuseppina Cantarella and Elena Fumagalli and Sara Barbera and Alfredo Cagnotto and {De Luigi}, Ada and Rossella Tonelli and Renato Bernardini and Tiziana Borsello and Tiziana Mennini",

year = "2008",

month = mar,

doi = "10.1016/j.nbd.2007.11.005",

language = "English",

volume = "29",

pages = "465--476",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press Inc.",

number = "3",

}

Bigini, P, Repici, M, Cantarella, G, Fumagalli, E, Barbera, S, Cagnotto, A, De Luigi, A, Tonelli, R, Bernardini, R, Borsello, T & Mennini, T 2008, 'Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse', Neurobiology of Disease, vol. 29, no. 3, pp. 465-476. https://doi.org/10.1016/j.nbd.2007.11.005

TY - JOUR

T1 - Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse

AU - Bigini, Paolo

AU - Repici, Mariaelena

AU - Cantarella, Giuseppina

AU - Fumagalli, Elena

AU - Barbera, Sara

AU - Cagnotto, Alfredo

AU - De Luigi, Ada

AU - Tonelli, Rossella

AU - Bernardini, Renato

AU - Borsello, Tiziana

AU - Mennini, Tiziana

PY - 2008/3

Y1 - 2008/3

N2 - 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.

AB - 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.

KW - Amyotrophic Lateral Sclerosis/genetics

KW - Animals

KW - Cell Count/methods

KW - Disease Progression

KW - Female

KW - Humans

KW - Male

KW - Mice

KW - Mice, Neurologic Mutants

KW - Motor Neurons/drug effects

KW - Receptors, Tumor Necrosis Factor, Type I/administration & dosage

KW - Recombinant Proteins/administration & dosage

KW - Tumor Necrosis Factor Decoy Receptors/administration & dosage

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors

UR - https://www.sciencedirect.com/science/article/pii/S0969996107002513?via%3Dihub

U2 - 10.1016/j.nbd.2007.11.005

DO - 10.1016/j.nbd.2007.11.005

M3 - Article

C2 - 18201889

SN - 0969-9961

VL - 29

SP - 465

EP - 476

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 3

ER -

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

Abstract

Keywords

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