Impact of Genetic Reduction of NMNAT2 on Chemotherapy-Induced Losses in Cell Viability In Vitro and Peripheral Neuropathy In Vivo

PloS One
Richard A SlivickiAndrea G Hohmann

Abstract

Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of ...Continue Reading

References

Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·P B Schiff, S B Horwitz
Jul 1, 1994·Archives of Neurology·Z SahenkJ R Mendell
Feb 4, 2010·PLoS Biology·Jonathan Gilley, Michael P Coleman
Aug 16, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jonathan GilleyMichael P Coleman
Aug 24, 2013·Trends in Neurosciences·Yousuf O AliHui-Chen Lu
Nov 29, 2013·Bioarchitecture·Stefan MildeMichael P Coleman
Jan 18, 2014·Bioorganic & Medicinal Chemistry·Kurt R BrundenCarlo Ballatore
Oct 18, 2014·Acta Neuropathologica·Hao ChiangBruce D Trapp
Dec 6, 2014·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Dwight MoulinUNKNOWN Canadian Pain Society
Jan 27, 2015·Neuroscience Letters·Christopher R Cashman, Ahmet Höke

❮ Previous
Next ❯

Citations

May 3, 2018·Disease Models & Mechanisms·Jennifer M BrazillR Grace Zhai
Oct 19, 2017·The Journal of Pharmacology and Experimental Therapeutics·S Lauren KyteDavid A Gewirtz
May 10, 2017·Journal of the Peripheral Nervous System : JPNS·Elliot TurkiewAhmet Höke
Apr 22, 2017·Scientific Reports·Lawrence M CareyAndrea G Hohmann
Jul 28, 2021·Acta Oncologica·Cornelia J C VermeerNiels Eijkelkamp

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
electrophoresis

Software Mentioned

GraphPad Prism
Revelation Quicklink
SPSS
ImageJ

Related Concepts

Related Feeds

Acute viral rhinopharyngitis

Acute viral rhinopharyngitis, also known as "common cold", is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Discover the latest research on acute viral rhinopharyngitis here.

Axonal Neuropathies

Axonal Neuropathy refers to disease or dysfunction of nerves caused as a result of damage or degeneration of axons. Here is the latest research.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.