Reactive Oxygen Species-mediated Neurodegeneration is Independent of the Ryanodine Receptor in

Overview

Journal J S C Acad Sci

Date 2016 Aug 20

PMID 27540332

Citations 3

Authors

Lyndsay Ea Young

Daniel C Williams

Affiliations

Soon will be listed here.

Abstract

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene , which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca) signaling in neurodegeneration. We tested the requirement for in ROS-mediated neurodegeneration using the genetically encoded photosensitizer KillerRed. Upon illumination of KillerRed expressing animals to produce ROS, we observed similar levels of degeneration in wild-type and mutant strains. Our results indicate that ROS-mediated cell death is independent of and suggest multiple molecular pathways of neurodegeneration.

Citing Articles

The Role of Ca Signaling in Aging and Neurodegeneration: Insights from Models.

Alvarez J, Alvarez-Illera P, Garcia-Casas P, Fonteriz R, Montero M Cells. 2020; 9(1).

PMID: 31947609 PMC: 7016793. DOI: 10.3390/cells9010204.

Genetic analysis of KillerRed in C. elegans identifies a shared role of calcium genes in ROS-mediated neurodegeneration.

Young L, Shoben C, Ricci K, Williams D J Neurogenet. 2018; 33(1):1-9.

PMID: 30489172 PMC: 6486406. DOI: 10.1080/01677063.2018.1531857.

Partitioning of naturally-occurring radionuclides (NORM) in Marcellus Shale produced fluids influenced by chemical matrix.

Nelson A, Johns A, Eitrheim E, Knight A, Basile M, Bettis 3rd E Environ Sci Process Impacts. 2016; 18(4):456-63.

PMID: 26952871 PMC: 5538885. DOI: 10.1039/c5em00540j.

References

Stiernagle T . Maintenance of C. elegans. WormBook. 2007; :1-11. PMC: 4781397. DOI: 10.1895/wormbook.1.101.1. View

Alexander A, Marfil V, Li C . Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases. Front Genet. 2014; 5:279. PMC: 4155875. DOI: 10.3389/fgene.2014.00279. View

Azevedo F, Carvalho L, Grinberg L, Farfel J, Ferretti R, Leite R . Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009; 513(5):532-41. DOI: 10.1002/cne.21974. View

Maryon E, Coronado R, Anderson P . unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction. J Cell Biol. 1996; 134(4):885-93. PMC: 2120954. DOI: 10.1083/jcb.134.4.885. View

Li J, Le W . Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp Neurol. 2013; 250:94-103. DOI: 10.1016/j.expneurol.2013.09.024. View

McIntire S, Reimer R, Schuske K, EDWARDS R, Jorgensen E . Identification and characterization of the vesicular GABA transporter. Nature. 1997; 389(6653):870-6. DOI: 10.1038/39908. View

Bulina M, Chudakov D, Britanova O, Yanushevich Y, Staroverov D, Chepurnykh T . A genetically encoded photosensitizer. Nat Biotechnol. 2005; 24(1):95-9. DOI: 10.1038/nbt1175. View

Xie A, Gao J, Xu L, Meng D . Shared mechanisms of neurodegeneration in Alzheimer's disease and Parkinson's disease. Biomed Res Int. 2014; 2014:648740. PMC: 4037122. DOI: 10.1155/2014/648740. View

Hall D, Gu G, Garcia-Anoveros J, Gong L, Chalfie M, Driscoll M . Neuropathology of degenerative cell death in Caenorhabditis elegans. J Neurosci. 1997; 17(3):1033-45. PMC: 6573168. View

10.

McIntire S, Jorgensen E, Kaplan J, Horvitz H . The GABAergic nervous system of Caenorhabditis elegans. Nature. 1993; 364(6435):337-41. DOI: 10.1038/364337a0. View

11.

Driscoll M, Chalfie M . The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature. 1991; 349(6310):588-93. DOI: 10.1038/349588a0. View

12.

Chang Y, Kong Q, Shan X, Tian G, Ilieva H, Cleveland D . Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS. PLoS One. 2008; 3(8):e2849. PMC: 2481395. DOI: 10.1371/journal.pone.0002849. View

13.

Earls L, Hacker M, Watson J, Miller 3rd D . Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration. Proc Natl Acad Sci U S A. 2010; 107(32):14460-5. PMC: 2922603. DOI: 10.1073/pnas.0910630107. View

14.

Williams D, El Bejjani R, Ramirez P, Coakley S, Kim S, Lee H . Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed. Cell Rep. 2013; 5(2):553-63. PMC: 3877846. DOI: 10.1016/j.celrep.2013.09.023. View

15.

Schuske K, Beg A, Jorgensen E . The GABA nervous system in C. elegans. Trends Neurosci. 2004; 27(7):407-14. DOI: 10.1016/j.tins.2004.05.005. View

16.

Xu K, Tavernarakis N, Driscoll M . Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum. Neuron. 2001; 31(6):957-71. DOI: 10.1016/s0896-6273(01)00432-9. View

17.

Labunskyy V, Gladyshev V . Role of reactive oxygen species-mediated signaling in aging. Antioxid Redox Signal. 2012; 19(12):1362-72. PMC: 3791051. DOI: 10.1089/ars.2012.4891. View

18.

Chakraborty S, Bornhorst J, Nguyen T, Aschner M . Oxidative stress mechanisms underlying Parkinson's disease-associated neurodegeneration in C. elegans. Int J Mol Sci. 2013; 14(11):23103-28. PMC: 3856108. DOI: 10.3390/ijms141123103. View

19.

Syntichaki P, Xu K, Driscoll M, Tavernarakis N . Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature. 2002; 419(6910):939-44. DOI: 10.1038/nature01108. View

20.

Aggad D, Veriepe J, Tauffenberger A, Parker J . TDP-43 toxicity proceeds via calcium dysregulation and necrosis in aging Caenorhabditis elegans motor neurons. J Neurosci. 2014; 34(36):12093-103. PMC: 4262699. DOI: 10.1523/JNEUROSCI.2495-13.2014. View