Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity.
Axon degeneration is an active program of self-destruction observed in many physiological and pathological settings. There are three Nicotinamide mononucleotide adenylyl transferase (Nmnat, EC2.7.7.1) in mammals. Overexpression of Nmnat1 or Nmnat3 can delay axon degeneration, while the role of Nmnat2 in axon degeneration remains largely unknown. Here we found that Nmnat2 was specifically and highly expressed in brain compared with Nmnat1 and Nmnat3. Furthermore, we found brain Nmnat2 was correlated with Alzheimer's disease in APPswe/PS1dE9 transgenic mice. Nmnat2 delayed Wallerian degeneration in cultured superior cervical ganglia (SCGs) from morphological changes, microtubule destruction and neurofilament degradation, mutation of the conserved enzyme activity site in Nmnat2 disrupted its enzyme activity as well as the axon-protective function. Our results demonstrate that the brain-specific Nmnat2 delays injury-induced axon degeneration dependent on its NAD synthesis activity. These findings provide new clues to further study the molecular mechanisms of axon degeneration and the related neurodegenerative diseases.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China.
Tingting
T
Yan
Yan
Y
Feng
Jin
J
Zheng
Xinjian
X
Ge
Yi
Y
Zhang
Dongmei
D
Wu
Jian
J
Zhao
Qiwei
Q
Zhai
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D009243:NAD / Q000096:biosynthesis*; D016900:Neurofilament Proteins / Q000378:metabolism; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D016900:Neurofilament Proteins; D009243:NAD; C484008:NMNAT2 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase