Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models

Shinjiro Kaneko, Jing Wang, Marie Kaneko, Glenn C Yiu, Joanna M. Hurrell, Tanuja Chitnis, Samia J. Khoury, Zhigang He

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Axonal damage is a major morphological alteration in the CNS of patients with multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for the axonal damage associated with MS/EAE and its contribution to the clinical symptoms remain unclear. The expression of a fusion protein, named "Wallerian degeneration slow" (Wlds), can protect axons from degeneration, likely through a β-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced with EAE, Wlds mice showed a modest attenuation of behavioral deficits and axon loss, suggesting that EAE-associated axon damage may occur by a mechanism similar to Wallerian degeneration. Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits in EAE models. Finally, we demonstrate that delayed NAm treatment is also beneficial to EAE models, pointing to the therapeutic potential of NAm as a protective agent for EAE and perhaps MS patients.

Original languageEnglish (US)
Pages (from-to)9794-9804
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number38
DOIs
StatePublished - Sep 20 2006
Externally publishedYes

Keywords

  • Axon degeneration
  • EAE
  • NAD
  • Nicotinamide
  • Wallerian degeneration
  • Wld

ASJC Scopus subject areas

  • Neuroscience(all)

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