Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nagaraj, Vini, Theis, Thomas, Johal, Anmol Singh, Seth, Arihant, Gore, Jada, Arsha, Neha, Patel, Mukti, Hao, Helen Baixia, Kurian, Nikki, Schachner, Melitta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432704/
https://www.ncbi.nlm.nih.gov/pubmed/32751444
http://dx.doi.org/10.3390/ijms21155417
_version_ 1783571855813115904
author Nagaraj, Vini
Theis, Thomas
Johal, Anmol Singh
Seth, Arihant
Gore, Jada
Arsha, Neha
Patel, Mukti
Hao, Helen Baixia
Kurian, Nikki
Schachner, Melitta
author_facet Nagaraj, Vini
Theis, Thomas
Johal, Anmol Singh
Seth, Arihant
Gore, Jada
Arsha, Neha
Patel, Mukti
Hao, Helen Baixia
Kurian, Nikki
Schachner, Melitta
author_sort Nagaraj, Vini
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7432704
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74327042020-08-27 Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth Nagaraj, Vini Theis, Thomas Johal, Anmol Singh Seth, Arihant Gore, Jada Arsha, Neha Patel, Mukti Hao, Helen Baixia Kurian, Nikki Schachner, Melitta Int J Mol Sci Article 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. MDPI 2020-07-30 /pmc/articles/PMC7432704/ /pubmed/32751444 http://dx.doi.org/10.3390/ijms21155417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagaraj, Vini
Theis, Thomas
Johal, Anmol Singh
Seth, Arihant
Gore, Jada
Arsha, Neha
Patel, Mukti
Hao, Helen Baixia
Kurian, Nikki
Schachner, Melitta
Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title_full Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title_fullStr Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title_full_unstemmed Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title_short Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
title_sort application of antibodies to neuronally expressed nogo-a increases neuronal survival and neurite outgrowth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432704/
https://www.ncbi.nlm.nih.gov/pubmed/32751444
http://dx.doi.org/10.3390/ijms21155417
work_keys_str_mv AT nagarajvini applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT theisthomas applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT johalanmolsingh applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT setharihant applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT gorejada applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT arshaneha applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT patelmukti applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT haohelenbaixia applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT kuriannikki applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth
AT schachnermelitta applicationofantibodiestoneuronallyexpressednogoaincreasesneuronalsurvivalandneuriteoutgrowth