Axonal Degeneration Is Blocked by Nicotinamide Mononucleotide Adenylyltransferase (Nmnat) Protein Transduction into Transected Axons

Yo Sasaki; Jeffrey Milbrandt

doi:10.1074/jbc.C110.193904

Axonal Degeneration Is Blocked by Nicotinamide Mononucleotide Adenylyltransferase (Nmnat) Protein Transduction into Transected Axons*

Yo Sasaki^‡ and
Jeffrey Milbrandt^‡^§,¹

From the ^‡Department of Genetics and
^§HOPE Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110

1 To whom correspondence should be addressed: 660 South Euclid Ave., Box 8118, St. Louis, MO 63110. Tel.: 314-362-4650; Fax: 314-362-8756; E-mail: jmilbrandt{at}wustl.edu.

Abstract

Axonal degeneration is an early and important component of many neurological disorders. Overexpression of nicotinamide mononucleotide adenylyltransferase (Nmnat), a component of the slow Wallerian degeneration (Wld^s) protein, protects axons from a variety of insults. We found that transduction of Nmnat protein into severed axons via virus-like particles prevented axonal degeneration. The post-injury efficacy of Nmnat indicates that its protective effects occur locally within the axon and provides an opportunity to develop novel agents to treat axonal damage.

Footnotes

↵* This work was supported, in whole or in part, by National Institutes of Health Grants NS070053 (to J. M.), AG13730 (to J. M.), NS065053 (to A. DiAntonio and J. M.). This work was also supported by Muscular Dystrophy Association Grants 10040 (to J. M.) and Craig H. Neilsen Foundation Grant 124030 (to J. M.). The authors and Washington University may derive benefit from a licensing agreement with Sirtris Pharmaceuticals, which did not provide any support for this work.
↵ The on-line version of this article (available at http://www.jbc.org) contains supplemental methods, videos 1 and 2, and Figs. 1–4.