Show simple item record

dc.contributor.authorManchon, Jose Felix Moruno
Uzor, Ndidi-Ese
Dabaghian, Yuri
Furr-Stimming, Erin E.
Finkbeiner, Steven
Tsvetkov, Andrey S.
dc.date.accessioned 2016-04-01T20:24:37Z
dc.date.available 2016-04-01T20:24:37Z
dc.date.issued 2015
dc.identifier.citation Manchon, Jose Felix Moruno, Uzor, Ndidi-Ese, Dabaghian, Yuri, et al.. "Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy." Scientific Reports, 5, (2015) ?Macmillan Publishers Limited: http://dx.doi.org/10.1038/srep15213.
dc.identifier.urihttps://hdl.handle.net/1911/88825
dc.description.abstract Autophagy is an important homeostatic mechanism that eliminates long-lived proteins, protein aggregates and damaged organelles. Its dysregulation is involved in many neurodegenerative disorders. Autophagy is therefore a promising target for blunting neurodegeneration. We searched for novel autophagic pathways in primary neurons and identified the cytosolic sphingosine-1-phosphate (S1P) pathway as a regulator of neuronal autophagy. S1P, a bioactive lipid generated by sphingosine kinase 1 (SK1) in the cytoplasm, is implicated in cell survival. We found that SK1 enhances flux through autophagy and that S1P-metabolizing enzymes decrease this flux. When autophagy is stimulated, SK1 relocalizes to endosomes/autophagosomes in neurons. Expression of a dominant-negative form of SK1 inhibits autophagosome synthesis. In a neuron model of Huntington's disease, pharmacologically inhibiting S1P-lyase protected neurons from mutant huntingtin-induced neurotoxicity. These results identify the S1P pathway as a novel regulator of neuronal autophagy and provide a new target for developing therapies for neurodegenerative disorders.
dc.language.iso eng
dc.publisher ?Macmillan Publishers Limited
dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.ᅠ
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.title Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy
dc.type Journal article
dc.contributor.funder University of Texas, Houston Medical School
dc.contributor.funder Hereditary Disease Foundation
dc.contributor.funder High Resolution Electron Microscopy Facility, University of Texas, MD Anderson Cancer Center
dc.contributor.funder National Institutes of Health
dc.contributor.funder Taube/Koret Center for Neurodegenerative Disease Research
dc.citation.journalTitle Scientific Reports
dc.citation.volumeNumber 5
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1038/srep15213
dc.identifier.pmcid PMC4609990
dc.identifier.pmid 26477494
dc.identifier.grantID CA16672 (High Resolution Electron Microscopy Facility, University of Texas, MD Anderson Cancer Center)
dc.identifier.grantID 3R01 NS039074 (National Institutes of Health)
dc.identifier.grantID NS083390 (National Institutes of Health)
dc.type.publication publisher version


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.ᅠ
Except where otherwise noted, this item's license is described as This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.ᅠ