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

被引：22

作者：

Bigini, Paolo ^{[1
]}

Repici, Mariaelena ^{[2
]}

Cantarella, Giuseppina ^{[3
]}

Fumagalli, Elena ^{[1
]}

Barbera, Sara ^{[1
]}

Cagnotto, Alfredo ^{[1
]}

De Luigi, Ada ^{[1
]}

Tonelli, Rossella ^{[1
]}

Bernardini, Renato ^{[3
]}

Borsello, Tiziana ^{[2
,4
]}

Mennini, Tiziana ^{[1
]}

机构：

[1] Inst Rich Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, I-20156 Milan, Italy

[2] Univ Lausanne, DBCM, CH-1005 Lausanne, Switzerland

[3] Univ Catania, Dept Expt & Clin Pharmacol, I-95125 Catania, Italy

[4] Inst Rich Farmacol Mario Negri, Dept Neurosci, I-20156 Milan, Italy

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 29卷 / 03期

关键词：

TNFR1; rhTBP-1; p38MAPK; JNK; motor neuron degeneration; wobbler; amyotrophic lateral sclerosis; TNF-alpha; glial activation;

D O I：

10.1016/j.nbd.2007.11.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 A LS, 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. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：465 / 476

页数：12

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