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Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis
- Source :
- Theranostics
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervoussystem (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiplesclerosis (MS) is unknown. Methods: Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results: High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion: The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS. Refereed/Peer-reviewed
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
medicine.medical_treatment
Medicine (miscellaneous)
multiple sclerosis
Peripheral blood mononuclear cell
immune response
Multiple sclerosis
Mice
Immune system
Neurotrophic factors
Leukocytes
Animals
Humans
Medicine
antibodies
Protein Precursors
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
B cell
Brain-derived neurotrophic factor
business.industry
Experimental autoimmune encephalomyelitis
brain-derived neurotrophic factor
Brain
Immunotherapy
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
proBDNF
medicine.anatomical_structure
Spinal Cord
Case-Control Studies
Immunology
Leukocytes, Mononuclear
immunotherapy
business
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 11
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....a66d09cedf9c1cc086b9afd2a91e881c