Protecting Axonal Degeneration by Increasing Nicotinamide Adenine Dinucleotide Levels in Experimental Autoimmune Encephalomyelitis Models

• DOI: 10.1523/jneurosci.2116-06.2006
• Publication Date: 2006-09-20T18:01:31Z
• Authors: Shinjiro Kaneko; Jing Wang; Marie Kaneko; Glenn Yiu; Joanna M. Hurrell; Tanuja Chitnis; Samia J. Khoury; Zhigang He
• Keywords: Wallerian degeneration; Axonal Degeneration; Degeneration (medical)

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, underlying mechanism for axonal associated MS/EAE contribution to clinical symptoms remain unclear. The expression fusion protein, named "Wallerian degeneration slow" (Wld(S)), can protect axons from degeneration, likely through beta-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced EAE, Wld(S) mice showed modest attenuation behavioral deficits axon loss, suggesting that EAE-associated may occur by similar Wallerian degeneration. Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents demyelinated improves EAE models. Finally, demonstrate delayed NAm treatment also beneficial models, pointing therapeutic potential as protective agent perhaps MS patients.