Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

被引:1195
作者
Chen, MS
Huber, AB
van der Haar, ME
Frank, M
Schnell, L
Spillmann, AA
Christ, F
Schwab, ME [1 ]
机构
[1] Univ Zurich, Inst Brain Res, Dept Neuromorphol, CH-8057 Zurich, Switzerland
[2] Swiss Fed Inst Technol, CH-8057 Zurich, Switzerland
关键词
D O I
10.1038/35000219
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely Limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats(1-4). Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C), Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.
引用
收藏
页码:434 / 439
页数:6
相关论文
共 19 条
[1]   RECOVERY FROM SPINAL-CORD INJURY MEDIATED BY ANTIBODIES TO NEURITE GROWTH-INHIBITORS [J].
BREGMAN, BS ;
KUNKELBAGDEN, E ;
SCHNELL, L ;
DAI, HN ;
GAO, D ;
SCHWAB, ME .
NATURE, 1995, 378 (6556) :498-501
[2]   ANTIBODY AGAINST MYELIN-ASSOCIATED INHIBITOR OF NEURITE GROWTH NEUTRALIZES NONPERMISSIVE SUBSTRATE PROPERTIES OF CNS WHITE MATTER [J].
CARONI, P ;
SCHWAB, ME .
NEURON, 1988, 1 (01) :85-96
[3]   2 MEMBRANE-PROTEIN FRACTIONS FROM RAT CENTRAL MYELIN WITH INHIBITORY PROPERTIES FOR NEURITE GROWTH AND FIBROBLAST SPREADING [J].
CARONI, P ;
SCHWAB, ME .
JOURNAL OF CELL BIOLOGY, 1988, 106 (04) :1281-1288
[4]  
Chen M. S., 1999, Society for Neuroscience Abstracts, V25, P2030
[5]   Molecular cloning of a novel mouse gene with predominant muscle and neural expression [J].
Geisler, JG ;
Stubbs, LJ ;
Wasserman, WW ;
Mucenski, ML .
MAMMALIAN GENOME, 1998, 9 (04) :274-282
[6]   COMPARATIVE EXPRESSED-SEQUENCE-TAG ANALYSIS OF DIFFERENTIAL GENE-EXPRESSION PROFILES IN PC-12 CELLS BEFORE AND AFTER NERVE GROWTH-FACTOR TREATMENT [J].
LEE, NH ;
WEINSTOCK, KG ;
KIRKNESS, EF ;
EARLEHUGHES, JA ;
FULDNER, RA ;
MARMAROS, S ;
GLODEK, A ;
GOCAYNE, JD ;
ADAMS, MD ;
KERLAVAGE, AR ;
FRASER, CM ;
VENTER, JC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8303-8307
[7]   Cloning and preliminary characterization of a 121 kDa protein with multiple predicted C2 domains [J].
Morris, NJ ;
Ross, SA ;
Neveu, JM ;
Lane, WS ;
Lienhard, GE .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1999, 1431 (02) :525-530
[8]  
NAGASE T, 1998, DNA RES, V5, P169
[9]   Rat and chicken s-rex/NSP mRNA: Nucleotide sequence of main transcripts and expression of splice variants in rat tissues [J].
Ninkina, NN ;
Baka, ID ;
Buchman, VL .
GENE, 1997, 184 (02) :205-210
[10]  
ROEBROEK AJM, 1993, J BIOL CHEM, V268, P13439