Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8478503 | Molecular and Cellular Neuroscience | 2016 | 12 Pages |
Abstract
The Nogo-66 receptor (NgR1), a receptor for Nogo-A, contributes to the inhibition of axonal regeneration in the adult central nervous system after traumatic injuries. Thus, NgR1 has been considered a critical target in axon regeneration therapy. Here, we identified a specific NgR1 antagonist peptide (HIYTALV, named NAP2) which promotes neurite regeneration in vitro from a phage display heptapeptide library. NAP2 was co-localized with NgR1 on the surface of PC12 cells and cerebellar granule cells (CGCs) by immunofluorescence assay. Horseradish peroxidase (HRP)-streptavidin-biotin assay further showed that NAP2 binds to NgR1 and the dissociation constant (Kd) was 0.45 μM Functional analyses indicated that NAP2 could reduce the inhibitory effects of Nogo-66 on neurite outgrowth in differentiated PC12 cells and CGCs by blocking the Nogo-66-induced activation of Rho-associated coiled coil-containing protein kinase (ROCK), collapsin response mediator protein 2 (CRMP2) and myosin light chain (MLC). Taken together, the small molecule NgR1 antagonist peptide NAP2 (MW: 815.98 Da) has a potential ability in crossing blood brain barrier and will be a promising therapeutic agent for the treatment of spinal cord injury and neurodegenerative diseases.
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Authors
Zhongqing Sun, Xiaoyong Dai, Yu Li, Shuwen Jiang, Guofeng Lou, Qiaoyu Cao, Rendong Hu, Yadong Huang, Zhijian Su, Meiwan Chen, Huanmin Luo, Xi Lin, Jun Sun, Fei Xiao,