NMNATs, evolutionarily conserved neuronal maintenance factors

Trends Neurosci. 2013 Nov;36(11):632-40. doi: 10.1016/j.tins.2013.07.002. Epub 2013 Aug 20.


Proper brain function requires neuronal homeostasis over a range of environmental challenges. Neuronal activity, injury, and aging stress the nervous system, and lead to neuronal dysfunction and degeneration. Nevertheless, most organisms maintain healthy neurons throughout life, implying the existence of active maintenance mechanisms. Recent studies have revealed a key neuronal maintenance and protective function for nicotinamide mononucleotide adenylyl transferases (NMNATs). We review evidence that NMNATs protect neurons through multiple mechanisms in different contexts, and highlight functions that either require or are independent of NMNAT catalytic activity. We then summarize data supporting a role for NMNATs in neuronal maintenance and raise intriguing questions on how NMNATs preserve neuronal integrity and facilitate proper neural function throughout life.

Keywords: NAD; NMNAT; axonopathy; chaperone; neurodegeneration; neuronal maintenance; proteinopathies; synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biocatalysis
  • Evolution, Molecular*
  • Humans
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Nicotinamide Mononucleotide / metabolism*
  • Nucleotidyltransferases / metabolism*


  • Nicotinamide Mononucleotide
  • Nucleotidyltransferases
  • glutamine-synthetase adenylyltransferase