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

共 47 条

[1]

Barone FC, 2001, J PHARMACOL EXP THER, V296, P312

[2] Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis [J].

Beers, David R. ;

Henkel, Jenny S. ;

Xiao, Qin ;

Zhao, Weihua ;

Wang, Jinghong ;

Yen, Albert A. ;

Siklos, Laszlo ;

McKercher, Scott R. ;

Appel, Stanley H. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) :16021-16026

[3] Basic and clinical research on amyotrophic lateral sclerosis and other motor neuron disorders in Italy: recent findings and achievements from a network of laboratories [J].

Beghi, E ;

Mennini, T .

NEUROLOGICAL SCIENCES, 2004, 25 (Suppl 2) :S41-S60

[4]

Benigni F, 1996, J IMMUNOL, V157, P5563

[5] Glutamate transporters in the spinal cord of the wobbler mouse [J].

Bigini, P ;

Bastone, A ;

Mennini, T .

NEUROREPORT, 2001, 12 (09) :1815-1820

[6] Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice [J].

Bigini, Paolo ;

Gardoni, Fabrizio ;

Barbera, Sara ;

Cagnotto, Alfredo ;

Fumagalli, Elena ;

Longhi, Annalisa ;

Corsi, Massimiliano M. ;

Di Luca, Monica ;

Mennini, Tiziana .

BMC NEUROSCIENCE, 2006, 7 (1)

[7]

Bigini Paolo, 2004, Methods Mol Med, V98, P73

[8] ASTROCYTOSIS IN WOBBLER MOUSE SPINAL-CORD INVOLVES A POPULATION OF ASTROCYTES WHICH IS GLUTAMINE SYNTHETASE-NEGATIVE [J].

BLONDET, B ;

HANTAZAMBROISE, D ;

AITIKHLEF, A ;

CAMBIER, D ;

MURAWSKY, M ;

RIEGER, F .

NEUROSCIENCE LETTERS, 1995, 183 (03) :179-182

[9]

Boillée S, 2001, GLIA, V33, P277, DOI 10.1002/1098-1136(20010315)33:4<277::AID-GLIA1026>3.3.CO

[10]

2-P

← 1 2 3 4 5 →