Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy
Autophagosome
Sphingosine Kinase
DOI:
10.1038/srep15213
Publication Date:
2015-10-19T09:46:09Z
AUTHORS (6)
ABSTRACT
Autophagy is an important homeostatic mechanism that eliminates long-lived proteins, protein aggregates and damaged organelles. Its dysregulation involved in many neurodegenerative disorders. therefore a promising target for blunting neurodegeneration. We searched novel autophagic pathways primary neurons identified the cytosolic sphingosine-1-phosphate (S1P) pathway as regulator of neuronal autophagy. S1P, bioactive lipid generated by sphingosine kinase 1 (SK1) cytoplasm, implicated cell survival. found SK1 enhances flux through autophagy S1P-metabolizing enzymes decrease this flux. When stimulated, relocalizes to endosomes/autophagosomes neurons. Expression dominant-negative form inhibits autophagosome synthesis. In neuron model Huntington's disease, pharmacologically inhibiting S1P-lyase protected from mutant huntingtin-induced neurotoxicity. These results identify S1P provide new developing therapies
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (51)
CITATIONS (74)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....