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

Autor: Helen Baixia Hao, Jada Gore, Neha Arsha, Anmol Singh Johal, Melitta Schachner, Nikki Kurian, Arihant Seth, Thomas Theis, Mukti Patel, Vini Nagaraj
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Central Nervous System
Male
lcsh:Chemistry
Myelin
Mice
stress
0302 clinical medicine
antibody
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
Chemistry
Antibodies
Monoclonal
General Medicine
Computer Science Applications
Cell biology
Oligodendroglia
medicine.anatomical_structure
Female
Casein kinase 2
Signal transduction
Myelin Proteins
psychological phenomena and processes
signal transduction
neurite outgrowth
Neurite
medicine.drug_class
Cell Survival
Central nervous system
Neuronal Outgrowth
Monoclonal antibody
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
mental disorders
medicine
Neurites
Animals
Physical and Theoretical Chemistry
Protein kinase A
Molecular Biology
mouse
cell culture
Polysialic acid
Organic Chemistry
Peptide Fragments
Nerve Regeneration
030104 developmental biology
nervous system
lcsh:Biology (General)
lcsh:QD1-999
Nogo-A
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 5417, p 5417 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 15
ISSN: 1661-6596
1422-0067
Popis: 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.
Databáze: OpenAIRE
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