ArticleThe Journal of biological chemistry2020
A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Extracellular vesicle-based therapeutic strategies for spinal cord injury.Extracellular vesicles and circulating nucleic acids · 2026Review
- Roles for Exosomes from Various Cellular Sources in Spinal Cord Injury.Molecular neurobiology · 2025Review
- The Endoplasmic Reticulum and Its Contacts: Emerging Roles in Axon Development, Neurotransmission, and Degeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Article
- A New Paradigm in Spinal Cord Injury Therapy: from Cell-free Treatment to Engineering Modifications.CNS & neurological disorders drug targets · 2024Review
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
- Amino-terminal proteolytic fragment of the axon growth inhibitor Nogo-A (Rtn4A) is upregulated by injury and promotes axon regeneration.The Journal of biological chemistry · 2023Article
- Research progress in role of exosomes exosomes in mental disorders.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Extracellular Vesicles in Chronic Demyelinating Diseases: Prospects in Treatment and Diagnosis of Autoimmune Neurological Disorders.Life (Basel, Switzerland) · 2022Review
- The Cellular and Molecular Signature of ALS in Muscle.Journal of personalized medicine · 2022Review
- Augmented Expression ofIranian journal of public health · 2022Article
- Article
- Nogo-A Is a Potential Prognostic Marker for Spinal Cord Injury.Disease markers · 2022Article
- Potential of different cells-derived exosomal microRNA cargos for treating spinal cord injury.Journal of orthopaedic translation · 2021Review
- Electroacupuncture Inhibits Myelin Sheath Injury in the Internal Capsule After Focal Cerebral Infarction in Rats Through the Nogo-A/NgR Signaling Pathway.Medical science monitor basic research · 2021Article
- Extracellular Vesicles as an Emerging Frontier in Spinal Cord Injury Pathobiology and Therapy.Trends in neurosciences · 2021Review
- Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury.Frontiers in cell and developmental biology · 2021Review
- Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage.International journal of molecular sciences · 2020Review
- Nogo BACE jumps on the exosome.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Glial signals are known to inhibit axonal regeneration and functional recovery after mammalian central nervous system trauma, including spinal cord injury. Such signals include membrane-associated proteins of the oligodendrocyte plasma membrane and astrocyte-derived, matrix-associated proteins. Here, using cell lines and primary cortical neuron cultures, recombinant protein expression, immunoprecipitation and immunoblot assays, transmission EM of exosomes, and axon regeneration assays, we explored the secretion and activity of the myelin-associated neurite outgrowth inhibitor Nogo-A and observed exosomal release of a 24-kDa C-terminal Nogo-A fragment from cultured cells. We found that the cleavage site in this 1192-amino-acid-long fragment is located between amino acids 961-971. We also detected a Nogo-66 receptor (NgR1)-interacting Nogo-66 domain on the exosome surface. Enzyme inhibitor treatment and siRNA knockdown revealed that β-secretase 1 (BACE1) is the protease responsible for Nogo-A cleavage. Functionally, exosomes with the Nogo-66 domain on their surface potently inhibited axonal regeneration of mechanically injured cerebral cortex neurons from mice. Production of this fragment was observed in the exosomal fraction from neuronal tissue lysates after spinal cord crush injury of mice. We also noted that, relative to the exosomal marker Alix, a Nogo-immunoreactive, 24-kDa protein is enriched in exosomes 2-fold after injury. We conclude that membrane-associated Nogo-A produced in oligodendrocytes is processed proteolytically by BACE1, is released via exosomes, and is a potent diffusible inhibitor of regenerative growth in NgR1-expressing axons.
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Registered trials
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