Silencing Nogo-A promotes functional recovery in demyelinating disease

Yuhong Yang, Yue Liu, Ping Wei, Haiyan Peng, Ryan Winger, Rehana Z. Hussain, Li Hong Ben, Petra D. Cravens, Anne R. Gocke, Krishna Puttaparthi, Michael K. Racke, Dana M. McTigue, Amy E. Lovett-Racke

Research output: Contribution to journalArticle

Abstract

Objective: To determine if suppressing Nogo-A, an axonal inhibitory protein, will promote functional recovery in a murine model of multiple sclerosis (MS). Methods: A small interfering RNA was developed to specifically suppress Nogo-A (siRNA-NogoA). The siRNA-NogoA silencing effect was evaluated in vitro and in vivo via immunohistochemistry. The siRNA was administered intravenously in 2 models of experimental autoimmune encephalomyelitis (EAE). Axonal repair was measured by upregulation of GAP43. Enzyme-linked immunosorbent assay, flow cytometry, and 3H-thymidine incorporation were used to determine immunological changes in myelin-specific T cells in mice with EAE. Results: The siRNA-NogoA suppressed Nogo-A expression in vitro and in vivo. Systemic administration of siRNA-NogoA ameliorated EAE and promoted axonal repair, as demonstrated by enhanced GAP43+ axons in the lesions. Myelin-specific T-cell proliferation and cytokine production were unchanged in the siRNA-NogoA-treated mice. Interpretation: Silencing Nogo-A in EAE promotes functional recovery. The therapeutic benefit appears to be mediated by axonal growth and repair, and is not attributable to changes in the encephalitogenic capacity of the myelin-specific T cells. Silencing Nogo-A may be a therapeutic option for MS patients to prevent permanent functional deficits caused by immune-mediated axonal damage.

Original languageEnglish (US)
Pages (from-to)498-507
Number of pages10
JournalAnnals of Neurology
Volume67
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Demyelinating Diseases
Small Interfering RNA
Autoimmune Experimental Encephalomyelitis
Myelin Sheath
T-Lymphocytes
Multiple Sclerosis
Thymidine
Axons
Flow Cytometry
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Yang, Y., Liu, Y., Wei, P., Peng, H., Winger, R., Hussain, R. Z., ... Lovett-Racke, A. E. (2010). Silencing Nogo-A promotes functional recovery in demyelinating disease. Annals of Neurology, 67(4), 498-507. https://doi.org/10.1002/ana.21935

Silencing Nogo-A promotes functional recovery in demyelinating disease. / Yang, Yuhong; Liu, Yue; Wei, Ping; Peng, Haiyan; Winger, Ryan; Hussain, Rehana Z.; Ben, Li Hong; Cravens, Petra D.; Gocke, Anne R.; Puttaparthi, Krishna; Racke, Michael K.; McTigue, Dana M.; Lovett-Racke, Amy E.

In: Annals of Neurology, Vol. 67, No. 4, 04.2010, p. 498-507.

Research output: Contribution to journalArticle

Yang, Y, Liu, Y, Wei, P, Peng, H, Winger, R, Hussain, RZ, Ben, LH, Cravens, PD, Gocke, AR, Puttaparthi, K, Racke, MK, McTigue, DM & Lovett-Racke, AE 2010, 'Silencing Nogo-A promotes functional recovery in demyelinating disease', Annals of Neurology, vol. 67, no. 4, pp. 498-507. https://doi.org/10.1002/ana.21935
Yang Y, Liu Y, Wei P, Peng H, Winger R, Hussain RZ et al. Silencing Nogo-A promotes functional recovery in demyelinating disease. Annals of Neurology. 2010 Apr;67(4):498-507. https://doi.org/10.1002/ana.21935
Yang, Yuhong ; Liu, Yue ; Wei, Ping ; Peng, Haiyan ; Winger, Ryan ; Hussain, Rehana Z. ; Ben, Li Hong ; Cravens, Petra D. ; Gocke, Anne R. ; Puttaparthi, Krishna ; Racke, Michael K. ; McTigue, Dana M. ; Lovett-Racke, Amy E. / Silencing Nogo-A promotes functional recovery in demyelinating disease. In: Annals of Neurology. 2010 ; Vol. 67, No. 4. pp. 498-507.
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