NAP Protects Against Cyanide-related Microtubule Destruction

Overview

Journal J Neural Transm (Vienna)

Specialties Neurology
Physiology

Date 2009 Jun 25

PMID 19551468

Citations 7

Authors

Ilona Zemlyak

Robert Sapolsky

Illana Gozes

Affiliations

Soon will be listed here.

Abstract

The peptide NAP (NAPVSIPQ) was shown to protect neurons against a wide variety of insults. Particularly, NAP was shown to be neuroprotective in vitro against cyanide in hippocampal cultures and against oxygen-glucose deprivation in hippocampal and cortical neuronal cultures. Cyanide causes energy depletion in the cell and destroys the cytoskeleton, and NAP has been shown before to protect the microtubule cytoskeleton. The current study explored the effect of NAP on cyanide-induced microtubule destruction in cerebral cortical cultures. Sodium cyanide (6.8 mM) reduced the number of neurons containing intact microtubules as identified by bIII-tubulin immunostaining. When sodium cyanide was added together with NAP (10(-14)-10(-12) M), complete protection was observed. Although the primary site of action of cyanide is considered to be the mitochondria, the current results involve microtubule destruction by cyanide toxicity that is completely reversed by NAP treatment.

Citing Articles

The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter.

Zuhra K, Szabo C FEBS J. 2021; 289(9):2481-2515.

PMID: 34297873 PMC: 9291117. DOI: 10.1111/febs.16135.

ADNP: in search for molecular mechanisms and innovative therapeutic strategies for frontotemporal degeneration.

Gozes I, Ivashko-Pachima Y Front Aging Neurosci. 2015; 7:205.

PMID: 26578950 PMC: 4624849. DOI: 10.3389/fnagi.2015.00205.

Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity.

Kimani S, Moterroso V, Lasarev M, Kipruto S, Bukachi F, Maitai C Springerplus. 2013; 2:647.

PMID: 24349951 PMC: 3862856. DOI: 10.1186/2193-1801-2-647.

The ADNP derived peptide, NAP modulates the tubulin pool: implication for neurotrophic and neuroprotective activities.

Oz S, Ivashko-Pachima Y, Gozes I PLoS One. 2012; 7(12):e51458.

PMID: 23272107 PMC: 3522725. DOI: 10.1371/journal.pone.0051458.

D-NAP prophylactic treatment in the SOD mutant mouse model of amyotrophic lateral sclerosis: review of discovery and treatment of tauopathy.

Jouroukhin Y, Ostritsky R, Gozes I J Mol Neurosci. 2012; 48(3):597-602.

PMID: 22956189 DOI: 10.1007/s12031-012-9882-6.

References

Ernesto M, Paula Cardoso A, Nicala D, Mirione E, Massaza F, Cliff J . Persistent konzo and cyanogen toxicity from cassava in northern Mozambique. Acta Trop. 2002; 82(3):357-62. DOI: 10.1016/s0001-706x(02)00042-6. View

Gozes I, Divinski I . NAP, a neuroprotective drug candidate in clinical trials, stimulates microtubule assembly in the living cell. Curr Alzheimer Res. 2008; 4(5):507-9. DOI: 10.2174/156720507783018208. View

Spong C, Abebe D, Gozes I, Brenneman D, Hill J . Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther. 2001; 297(2):774-9. View

Shepherd G, Velez L . Role of hydroxocobalamin in acute cyanide poisoning. Ann Pharmacother. 2008; 42(5):661-9. DOI: 10.1345/aph.1K559. View

Collman J, Dey A, Decreau R, Yang Y, Hosseini A, Solomon E . Interaction of nitric oxide with a functional model of cytochrome c oxidase. Proc Natl Acad Sci U S A. 2008; 105(29):9892-6. PMC: 2481353. DOI: 10.1073/pnas.0804257105. View

Wagner O, Lifshitz J, Janmey P, Linden M, McIntosh T, Leterrier J . Mechanisms of mitochondria-neurofilament interactions. J Neurosci. 2003; 23(27):9046-58. PMC: 6740819. View

Ray P, Monroe F, Berman J, Fiedler J . Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. Neurochem Res. 1991; 16(10):1121-4. DOI: 10.1007/BF00966589. View

Zemlyak I, Manley N, Sapolsky R, Gozes I . NAP protects hippocampal neurons against multiple toxins. Peptides. 2007; 28(10):2004-8. DOI: 10.1016/j.peptides.2007.08.004. View

Escobar-Khondiker M, Hollerhage M, Muriel M, Champy P, Bach A, Depienne C . Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. J Neurosci. 2007; 27(29):7827-37. PMC: 6672878. DOI: 10.1523/JNEUROSCI.1644-07.2007. View

10.

Schulz J, Henshaw D, MacGarvey U, Beal M . Involvement of oxidative stress in 3-nitropropionic acid neurotoxicity. Neurochem Int. 1996; 29(2):167-71. DOI: 10.1016/0197-0186(95)00122-0. View

11.

Alexi T, Hughes P, Faull R, Williams C . 3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration. Neuroreport. 1998; 9(11):R57-64. DOI: 10.1097/00001756-199808030-00001. View

12.

Zamostiano R, Pinhasov A, Gelber E, Steingart R, Seroussi E, Giladi E . Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem. 2000; 276(1):708-14. DOI: 10.1074/jbc.M007416200. View

13.

Shiryaev N, Jouroukhin Y, Giladi E, Polyzoidou E, Grigoriadis N, Rosenmann H . NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model. Neurobiol Dis. 2009; 34(2):381-8. DOI: 10.1016/j.nbd.2009.02.011. View

14.

Mattson M, PARTIN J . Evidence for mitochondrial control of neuronal polarity. J Neurosci Res. 1999; 56(1):8-20. DOI: 10.1002/(SICI)1097-4547(19990401)56:1<8::AID-JNR2>3.0.CO;2-G. View

15.

Vulih-Shultzman I, Pinhasov A, Mandel S, Grigoriadis N, Touloumi O, Pittel Z . Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J Pharmacol Exp Ther. 2007; 323(2):438-49. DOI: 10.1124/jpet.107.129551. View

16.

Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-59. DOI: 10.1007/BF00308809. View

17.

Rotstein M, Bassan H, Kariv N, Speiser Z, Harel S, Gozes I . NAP enhances neurodevelopment of newborn apolipoprotein E-deficient mice subjected to hypoxia. J Pharmacol Exp Ther. 2006; 319(1):332-9. DOI: 10.1124/jpet.106.106898. View

18.

Zemlyak I, Furman S, Brenneman D, Gozes I . A novel peptide prevents death in enriched neuronal cultures. Regul Pept. 2000; 96(1-2):39-43. DOI: 10.1016/s0167-0115(00)00198-1. View

19.

Pinhasov A, Mandel S, Torchinsky A, Giladi E, Pittel Z, Goldsweig A . Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res Dev Brain Res. 2003; 144(1):83-90. DOI: 10.1016/s0165-3806(03)00162-7. View

20.

Fatokun A, Smith R, Stone T . Resistance to kynurenic acid of the NMDA receptor-dependent toxicity of 3-nitropropionic acid and cyanide in cerebellar granule neurons. Brain Res. 2008; 1215:200-7. DOI: 10.1016/j.brainres.2008.04.013. View