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

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

研究成果: Article査読

124 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)9794-9804
ページ数11
ジャーナルJournal of Neuroscience
26
38
DOI
出版ステータスPublished - 20-09-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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