LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury

被引：164

作者：

Ji, Benxiu

Li, Mingwei

Wu, Wu-Tian

Yick, Leung-Wah

Lee, Xinhua

Shao, Zhaohui

Wang, Joy

So, Kwok-Fai

McCoy, John M.

Pepinsky, R. Blake

Mi, Sha

Relton, Jane K.

机构：

[1] Biogen Inc, Cambridge, MA 02142 USA

[2] Univ Hong Kong, Fac Med, Dept Anat, Hong Kong, Hong Kong, Peoples R China

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2006年 / 33卷 / 03期

关键词：

D O I：

10.1016/j.mcn.2006.08.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

LINGO-1 is a CNS-specific protein and a functional component of the NgR1/p75/LINGO-1 and NgR1/TAJ(TROY)/LINGO-1 signaling complexes that mediate inhibition of axonal outgrowth. These receptor complexes mediate the axonal growth inhibitory effects of Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp) via RhoA activation. Soluble LINGO-1 (LINGO-1-Fc), which acts as an antagonist of these pathways by blocking LINGO-1 binding to NgR1, was administered to rats after dorsal or lateral hemisection of the spinal cord. LINGO-1-Fc treatment significantly improved functional recovery, promoted axonal sprouting and decreased RhoA activation and increased oligodendrocyte and neuronal survival after either rubrospinal or corticospinal tract transection. These experiments demonstrate an important role for LINGO-1 in modulating axonal outgrowth in vivo and that treatment with LINGO-1-Fc can significantly enhance recovery after spinal cord injury. (c) 2006 Elsevier Inc. All rights reserved.

引用

收藏

页码：311 / 320

页数：10

相关论文

共 55 条

[41] Neurobiology - Inhibitor of neurite outgrowth in humans [J].

Prinjha, R ;

Moore, SE ;

Vinson, M ;

Blake, S ;

Morrow, R ;

Christie, G ;

Michlovich, D ;

Simmons, DL ;

Walsh, FS .

NATURE, 2000, 403 (6768) :383-384

[42] Plasticity of motor systems after incomplete spinal cord injury [J].

Raineteau, O ;

Schwab, ME .

NATURE REVIEWS NEUROSCIENCE, 2001, 2 (04) :263-273

[43] Reorganization of descending motor tracts in the rat spinal cord [J].

Raineteau, O ;

Fouad, K ;

Bareyre, FM ;

Schwab, ME .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2002, 16 (09) :1761-1771

[44] Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton [J].

Ren, XD ;

Kiosses, WB ;

Schwartz, MA .

EMBO JOURNAL, 1999, 18 (03) :578-585

[45] Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury [J].

Ruitenberg, MJ ;

Blits, B ;

Dijkhuizen, PA ;

te Beek, ET ;

Bakker, A ;

van Heerikhuize, JJ ;

Pool, CW ;

Hermens, WTJ ;

Boer, GJ ;

Verhaagen, J .

NEUROBIOLOGY OF DISEASE, 2004, 15 (02) :394-406

[46] TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration [J].

Shao, ZH ;

Browning, JL ;

Lee, XH ;

Scott, ML ;

Shulga-Morskaya, S ;

Allaire, N ;

Thill, G ;

Levesque, M ;

Sah, D ;

McCoy, JM ;

Murray, B ;

Jung, V ;

Pepinsky, RB ;

Mi, S .

NEURON, 2005, 45 (03) :353-359

[47] Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury [J].

Springer J.E. ;

Azbill R.D. ;

Knapp P.E. .

Nature Medicine, 1999, 5 (8) :943-946

[48] Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury [J].

Stirling, DP ;

Khodarahmi, K ;

Liu, J ;

McPhail, LT ;

McBride, CB ;

Steeves, JD ;

Ramer, MS ;

Tetzlaff, W .

JOURNAL OF NEUROSCIENCE, 2004, 24 (09) :2182-2190

[49] Neurite growth inhibitors restrict plasticity and functional recovery following corticospinal tract lesions [J].

Thallmair, M ;

Metz, GAS ;

Z'Graggen, WJ ;

Raineteau, O ;

Kartje, GL ;

Schwab, ME .

NATURE NEUROSCIENCE, 1998, 1 (02) :124-131

[50] p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp [J].

Wang, KC ;

Kim, JA ;

Sivasankaran, R ;

Segal, R ;

He, ZG .

NATURE, 2002, 420 (6911) :74-78

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