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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Alteration of sphingosine kinases is responsible for alpha synuclein secretion and for cells death in experimental model of Parkinson Disease

Meeting Abstract

  • Joanna Strosznajder - Mossakowski Medical Research Centre Polish Academy of Sciences, Cellular Signalling Dept., Warsaw, Poland
  • presenting/speaker Joanna Pyszko - Mossakowski Medical Research Centre Polish Academy of Sciences, Cellular Signalling Dept., Warsaw, Poland
  • Magdalena Gassowska - Mossakowski Medical Research Centre Polish Academy of Sciences, Cellular Signalling Dept., Warsaw, Poland
  • Anna Kazmierczak - Mossakowski Medical Research Centre Polish Academy of Sciences, Cellular Signalling Dept., Warsaw, Poland
  • Robert Strosznajder - Mossakowski Medical Research Centre Polish Academy of Sciences, Neurosurgery Dept., Warsaw, Poland
  • Agata Adamczyk - Mossakowski Medical Research Centre Polish Academy of Sciences, Cellular Signalling Dept., Warsaw, Poland

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP4.12

DOI: 10.3205/12dgnn089, URN: urn:nbn:de:0183-12dgnn0896

Published: September 11, 2012

© 2012 Strosznajder et al.
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Outline

Text

Bioactive sphingolipids are important molecules that control wide repertoire of neuronal processes including neurotransmission, synaptic function cells proliferation and death. Diverse stimuli and several pathological conditions affects sphingolipids metabolism. Sphingosine kinases (SKI/II) are conserved enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P) which acts as a primary and secondary messenger. The role of biosphingolipids in pathogenesis of Parkinson Diseases (PD) is unknown. Our study indicating that inhibition of SK(s) leads to secretion of alpha synuclein (ASN) from nerve endings fraction. Then it was observed that extracelullarly acting ASN in oligomeric form can exert toxicity by modulation of dopamine transporter, enhancement of NMDA receptor mediated nitric oxide signaling and its interaction with several proteins. It was described previously that ASN is accumulated in the form of Levy bodies in neuronal cells in PD. Mutations in ASN gene were found to be responsible for the familiar form of PD and the alteration of ASN structure and concentration could be involve in pathogenesis of sporadic form of PD. We have found that extracelullarly acting ASN in oligomeric form and in concentration dependent manner induces oxidative stress in dopaminergic PC12 cells and inhibits expression of SKI. ASN decreases also gene expression for S1P receptor 1. The inhibitor of SKI and antagonist of S1PR1 influence significantly in a dose dependent manner dopaminergic cells viability. Our data presented the vicious circle between SK and ASN that could be crucial for PD pathogenesis. The 1-methyl-4-phenylpyridinium (MPP+) widely used compound for induction of PD experimental model evokes PC12/SH-SY5Y cells death by 20-50% in time dependent manner and inhibits SKI. MPP+ alters sphingolipids signaling leading to caspase dependent apoptotic cells death. S1P enhances survival of these cells and can offer novel protective strategy in PD.