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Citation
Tang, B.L. (2019). Why is NMNAT Protective against Neuronal Cell Death and Axon Degeneration, but Inhibitory of Axon Regeneration?  Cells 8(3): E267.
FlyBase ID
FBrf0241829
Publication Type
Review
Abstract

Nicotinamide mononucleotide adenylyltransferase (NMNAT), a key enzyme for NAD⁺ synthesis, is well known for its activity in neuronal survival and attenuation of Wallerian degeneration. Recent investigations in invertebrate models have, however, revealed that NMNAT activity negatively impacts upon axon regeneration. Overexpression of Nmnat in laser-severed Drosophila sensory neurons reduced axon regeneration, while axon regeneration was enhanced in injured mechanosensory axons in C. elegansnmat-2 null mutants. These diametrically opposite effects of NMNAT orthologues on neuroprotection and axon regeneration appear counterintuitive as there are many examples of neuroprotective factors that also promote neurite outgrowth, and enhanced neuronal survival would logically facilitate regeneration. We suggest here that while NMNAT activity and NAD⁺ production activate neuroprotective mechanisms such as SIRT1-mediated deacetylation, the same mechanisms may also activate a key axonal regeneration inhibitor, namely phosphatase and tensin homolog (PTEN). SIRT1 is known to deacetylate and activate PTEN which could, in turn, suppress PI3 kinase⁻mTORC1-mediated induction of localized axonal protein translation, an important process that determines successful regeneration. Strategic tuning of Nmnat activity and NAD⁺ production in axotomized neurons may thus be necessary to promote initial survival without inhibiting subsequent regeneration.

PubMed ID
PubMed Central ID
PMC6468476 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cells
    Title
    Cells
    ISBN/ISSN
    2073-4409
    Data From Reference
    Genes (2)