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Type: Journal article
Title: Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis
Author: Hu, Z.-L.
Luo, C.
Hurtado, P.R.
Li, H.
Wang, S.
Hu, B.
Xu, J.-M.
Liu, Y.
Feng, S.-Q.
Hurtado-Perez, E.
Chen, K.
Zhou, X.-F.
Li, C.-Q.
Dai, R.-P.
Citation: Theranostics, 2021; 11(2):715-730
Publisher: Ivyspring International Publisher
Issue Date: 2021
ISSN: 1838-7640
Statement of
Zhao-Lan Hu, Cong Luo, Plinio Reinaldo Hurtado, Hui Li, Shuang Wang, Bo Hu ... et al.
Abstract: Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervous system (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiple sclerosis (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.
Keywords: Multiple sclerosis; brain-derived neurotrophic factor; proBDNF; antibodies, immunotherapy; B cell; immune response
Rights: © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
DOI: 10.7150/thno.51390
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