Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth

• Published in: International journal of molecular sciences 2020-07, Vol.21 (15), p.5417
• Main Authors: Nagaraj, Vini, Theis, Thomas, Johal, Anmol Singh, Seth, Arihant, Gore, Jada, Arsha, Neha, Patel, Mukti, Hao, Helen Baixia, Kurian, Nikki, Schachner, Melitta
• Format: Article
• Language: English
• Subjects: Ablation; Acids; Animals; Antibodies, Monoclonal - metabolism; antibody; Axon sprouting; Axonogenesis; Axons; Casein; Casein kinase II; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; cell culture; Cell Survival; Cells, Cultured; Central nervous system; Central Nervous System - injuries; Cerebellum; Experiments; Female; Fyn protein; Granule cells; Injury prevention; Male; Mammals; Mice; Monoclonal antibodies; mouse; Myelin; Myelin Proteins - antagonists & inhibitors; Myelin Proteins - metabolism; Nerve Regeneration; Nervous system; neurite outgrowth; Neurites - metabolism; Neurites - pathology; Neuronal Outgrowth; Neurons; Neutralizing; Nogo-A; Oligodendrocytes; Oligodendroglia - metabolism; Oligodendroglia - pathology; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - metabolism; Polyclonal antibodies; Polysialic acid; Protein kinase A; Regeneration; Signal transduction; Src protein; Studies; Survival
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155417

Nogo-A, a glycoprotein expressed in oligodendrocytes and central nervous system myelin, inhibits regeneration after injury. Antibodies against Nogo-A neutralize this inhibitory activity, improve locomotor recovery in spinal cord-injured adult mammals, and promote regrowth/sprouting/saving of damaged axons beyond the lesion site. Nogo-A is also expressed by neurons. Complete ablation of Nogo-A in all cell types expressing it has been found to lead to recovery in some studies but not in others. Neuronal ablation of Nogo-A reduces axonal regrowth after injury. In view of these findings, we hypothesized that, in addition to neutralizing Nogo-A in oligodendrocytes and myelin, Nogo-A antibodies may act directly on neuronal Nogo-A to trigger neurite outgrowth and neuronal survival. Here, we show that polyclonal and monoclonal antibodies against Nogo-A enhance neurite growth and survival of cultured cerebellar granule neurons and increase expression of the neurite outgrowth-promoting L1 cell adhesion molecule and polysialic acid. Application of inhibitors of signal transducing molecules, such as c-src, c-fyn, protein kinase A, and casein kinase II reduce antibody-triggered neurite outgrowth. These observations indicate that the recovery-promoting functions of antibodies against Nogo-A may not only be due to neutralizing Nogo-A in oligodendrocytes and myelin, but also to their interactions with Nogo-A on neurons.