NMNATs, evolutionarily conserved neuronal maintenance factors

Abstract

•Neurons require a 'maintenance plan' that enables them to endure daily wear and tear.•NMNATs function as NAD synthesizing enzymes and chaperones.•Loss of NMNAT causes rapid and severe neurodegeneration.•NMNATs have the broadest and most potent neuroprotective effects.•Alzheimer's Disease, Parkinson's Disease, and other neurodegenerative disorders are accompanied by downregulation of NMNAT. 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. © 2013 Elsevier Ltd.