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-α overexpression may contribute to motor neuron death in amyotrophic lateral sclerosis (ALS). We investigated the intracellular pathway associated with TNF-α in the wobbler mouse, a murine model of ALS, at the onset of symptoms. TNF-α 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-α was further confirmed by the protective effect of treatment with rhTNF-α 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-α and TNFR1 levels. rhTBP-1 might possibly bind TNF-α and reduce the downstream phosphorylation of two main effectors of the neuroinflammatory response, p38MAPK and JNK.
AB - TNF-α overexpression may contribute to motor neuron death in amyotrophic lateral sclerosis (ALS). We investigated the intracellular pathway associated with TNF-α in the wobbler mouse, a murine model of ALS, at the onset of symptoms. TNF-α 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-α was further confirmed by the protective effect of treatment with rhTNF-α 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-α and TNFR1 levels. rhTBP-1 might possibly bind TNF-α and reduce the downstream phosphorylation of two main effectors of the neuroinflammatory response, p38MAPK and JNK.
KW - Amyotrophic lateral sclerosis
KW - Glial activation
KW - JNK
KW - Motor neuron degeneration
KW - p38MAPK
KW - rhTBP-1
KW - TNF-α
KW - TNFR1
KW - Wobbler
UR - http://www.scopus.com/inward/record.url?scp=39249083637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39249083637&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2007.11.005
DO - 10.1016/j.nbd.2007.11.005
M3 - Article
C2 - 18201889
AN - SCOPUS:39249083637
VL - 29
SP - 465
EP - 476
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 3
ER -