Sphingosine-1-phosphate and its receptors signaling in neurodegeneration/neuroprotection

• Autorzy: Strosznajder J.B. , Motyl J. , Czubowicz K. , Strosznajder R.
• Języki publikacji: EN

Abstrakty

EN

Sphingosine -1-phosphate (S1P) is synthesized by sphingosine kinases (SphK1/2E.C. 2.7.1.91) and exerts its function as intracellular messenger or acts in an autocrine or paracrine fashion through specific G protein operated receptors (S1P1-S1P5). Depending on SphK type and its localization S1P may influence different cell functions. S1P synthesized by SphK1 is involved in cell survival while produced by SphK2 may activate death signaling. S1P is degraded by phosphohydrolyses and irreversibly by S1P lyase (SPL, E.C.4.1.2.27) which appears to be very important in sphingolipid homeostasis. The alterations of sphingolipid rheostat is suggested to be crucial in pathogenesis/pathomechanism of neurodegenerative disorders. In our study we have evaluated the SphKs and SPL expression/activity as well as the role of S1P in different types of oxidative stress involved in neurodegenerative disorders. Moreover, the implications of SphK/S1P in the cell models of Alzheimer’s disease induced by amyloid peptides (AB) and alfa synuclein (ASN) were determined. Oxidative stress alters SphKs and SPL expression, activity and cells viability. In AD model significant decrease of SphK expression and activity/lower S1P synthesis leads to series of the following consecutive events: oxidative stress, down regulation of antiapoptotic protein Bcl-2, up-regulation of pro-apoptotic BAX and HrK and finally to cell’s death. Exogenous S1P and the agonist(s) of S1P1 or S1P3 receptors exert cytoprotective effects which are mediated by PI3/ Akt signaling pathway and by regulation of Bcl2 proteins. Summarizing, our data suggest that S1P, its receptor(s) agonists and inhibitors of SPL should be considered in therapy of neurodegenerative disorders. Supported by NCN grant 5870/P01/2011/40

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S15-S16

Twórcy

autor

Strosznajder J.B.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Motyl J.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Czubowicz K.

• Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder R.

• Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland