Details

Autor(en) / Beteiligte

• Li, Weiwei
• Walus, Lee
• Rabacchi, Sylvia A
• Jirik, Adrienna
• Chang, Ernie
• Schauer, Jessica
• Zheng, Betty H
• Benedetti, Nancy J
• Liu, Betty P
• Choi, Eugene
• Worley, Dane
• Silvian, Laura
• Mo, Wenjun
• Mullen, Colleen
• Yang, Weixing
• Strittmatter, Stephen M
• Sah, Dinah W Y
• Pepinsky, Blake
• Lee, Daniel H S

Titel

A Neutralizing Anti-Nogo66 Receptor Monoclonal Antibody Reverses Inhibition of Neurite Outgrowth by Central Nervous System Myelin

Ist Teil von

• The Journal of biological chemistry, 2004-10, Vol.279 (42), p.43780-43788

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2004

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The Nogo66 receptor (NgR1) is a neuronal, leucinerich repeat (LRR) protein that binds three central nervous system (CNS) myelin proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, and mediates their inhibitory effects on neurite growth. Although the LRR domains on NgR1 are necessary for binding to the myelin proteins, the exact epitope(s) involved in ligand binding is unclear. Here we report the generation and detailed characterization of an anti-NgR1 monoclonal antibody, 7E11. The 7E11 monoclonal antibody blocks Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein binding to NgR1 with IC 50 values of 120, 14, and 4.5 n m , respectively, and effectively promotes neurite outgrowth of P3 rat dorsal root ganglia neurons cultured on a CNS myelin substrate. Further, we have defined the molecular epitope of 7E11 to be DNAQLR located in the third LRR domain of rat NgR1. Our data demonstrate that anti-NgR1 antibodies recognizing this epitope, such as 7E11, can neutralize CNS myelin-dependent inhibition of neurite outgrowth. Thus, specific anti-NgR1 antibodies may represent a useful therapeutic approach for promoting CNS repair after injury.