title: Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models.
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" (Wld(S)), can protect axons from degeneration, likely through a beta-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced with EAE, Wld(S) 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.
authors.affiliation: Division of Neuroscience, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Kaneko
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Marie
authors.initials: M
authors.lastname: Kaneko
authors.forename: Glenn
authors.initials: G
authors.lastname: Yiu
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Hurrell
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009243:NAD / Q000096:biosynthesis* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control
chemical_list: D018696:Neuroprotective Agents; D009243:NAD