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Identified 15 years ago, the Wlds mouse carries a spontaneous mutation that encodes a fusion protein with neuroprotective properties. In a Perspective, Simon discusses new work (Araki et al.) that identifies the Nmnat1 fragment of the fusion protein as mediating neuroprotection by boosting NAD biosynthesis and increasing the activity of the NAD-dependent deacetylase, SIRT1, a regulator of transcription.
A. Bedalov is in the Clinical Research Division and J. A. Simon is in the Clinical Research and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. E-mail: abedalov{at}fhcrc.org, jsimon{at}fhcrc.org
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