Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration
Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration
复制标题
DOI：
10.1126/science.1098014
复制
发表时间：
2004-08-13
期刊：
影响因子：
56.9
通讯作者：
Milbrandt, J
中科院分区：
文献类型：
--
作者：
Araki, T;Sasaki, Y;Milbrandt, J
Axonal degeneration is an active program of self-destruction that is observed in many physiological and pathological settings. In Wallerian degeneration slow (wld(s)) mice, Wallerian degeneration in response to axonal injury is delayed because of a mutation that results in overexpression of a chimeric protein (Wld(s)) composed of the ubiquitin assembly protein Ufd2a and the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme Nmnat1. We demonstrate that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein. Furthermore, we demonstrate that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased Nmnat activity that leads to axonal protection. These findings suggest that novel therapeutic strategies directed at increasing the supply of NAD and/or Sir2 activation may be effective for treatment of diseases characterized by axonopathy and neurodegeneration.
