A chimeric protein called Wallerian degeneration slow(Wld^(S))was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration.This provides a useful tool in elucidating the me...A chimeric protein called Wallerian degeneration slow(Wld^(S))was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration.This provides a useful tool in elucidating the mechanisms of axon degeneration.Over-expression of WldS attenuates the axon degeneration that is associated with several neurodegenerative disease models,suggesting a new logic for developing a potential protective strategy.At molecular level,although Wld^(S)is a fusion protein,the nicotinamide mononucleotide adenylyl transferase 1(Nmnat1)is required and sufficient for the protective effects of Wld^(S),indicating a critical role of NAD biosynthesis and perhaps energy metabolism in axon degeneration.These findings challenge the proposed model in which axon degeneration is operated by an active programmed process and thus may have important implication in understanding the mechanisms of neurodegeneration.In this review,we will summarize these recent findings and discuss their relevance to the mechanisms of axon degeneration.展开更多
基金This study was supported by grants from National Natural Science Foundation of China(30570558 and 30825009)National Basic Research Program of China(973 Program,2009CB918403 and 2007CB914501)Q.Zhai is a scholar of the Hundred Talents Program from Chinese Academy of Sciences,and a scholar of the Shanghai Rising-Star Program from Science and Technology Commission of Shanghai Municipality(08QH1402600).
文摘A chimeric protein called Wallerian degeneration slow(Wld^(S))was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration.This provides a useful tool in elucidating the mechanisms of axon degeneration.Over-expression of WldS attenuates the axon degeneration that is associated with several neurodegenerative disease models,suggesting a new logic for developing a potential protective strategy.At molecular level,although Wld^(S)is a fusion protein,the nicotinamide mononucleotide adenylyl transferase 1(Nmnat1)is required and sufficient for the protective effects of Wld^(S),indicating a critical role of NAD biosynthesis and perhaps energy metabolism in axon degeneration.These findings challenge the proposed model in which axon degeneration is operated by an active programmed process and thus may have important implication in understanding the mechanisms of neurodegeneration.In this review,we will summarize these recent findings and discuss their relevance to the mechanisms of axon degeneration.
