Ganglioside GM1 has demonstrated to attenuate Parkinson Disease (PD) symptoms in clinical and preclinical trials. Nevertheless, the GM1 efficacy revealed in vitro is critically reduced in vivo, because of the amphiphilic behavior that limits the passage across the blood brain barrier (BBB). In vitro and in vivo experiments showed that GM1 exerts neurotrophic functions by interacting with plasma membrane (PM) proteins throughout its oligosaccharide portion (OligoGM1). Furthermore, OligoGM1 intravenously or subcutaneously injected into mice is absorbed and taken up by different organs and tissues, including brain. In order to take advantage of GM1 oligosaccharide properties and to overcome GM1 pharmacological limitation, this study has been aimed by the investigation of the OligoGM1 transportthrough the BBB, by using a human in vitro model for human brain-like endothelial cells (hBLEC). Ruled out the toxicity of OligoGM1 on hBLEC, the OligoGM1 transport across the hBBB has been analyzed, finding out a 20 fold higher rate than GM1 and a time and concentration dependence. In order to characterize the OligoGM1 passage, a direct evaluation of the OligoGM1 interaction with the ABC-transporters was carried on, leaving out this way for OligoGM1 transport. Moreover, inverse- and 4°C-transport experiments were performed excluding the implication of the active transport for OligoGM1 passage across the hBLEC, leading to consider the passive-paracellular route. Furthermore, after the hBLEC transport, OligoGM1 maintained its stability and capacity to induce neuritogenesis in the mouse neuroblastoma cells line Neuro2a. This preliminary study has improved the knowledge about the GM1 pharmacological potential by proving that OligoGM1 can cross advantageously the BBB, offering a new promising therapeutic strategy.
Characterization of the GM1 oligosaccharide transport across the blood-brain-barrier / M. Maggioni, E. Di Biase, G. Lunghi, E. Sevin, F. Gosselet, E. Chiricozzi, S. Sonnino. - In: FEBS OPENBIO. - ISSN 2211-5463. - 8:Suppl. 1(2018 Jul), pp. P.14-017-Tue.368-P.14-017-Tue.368. ((Intervento presentato al 43. convegno FEBS Congress : from 7th to 12th July tenutosi a Prague (Czech Republic) nel 2018.
|Titolo:||Characterization of the GM1 oligosaccharide transport across the blood-brain-barrier|
MAGGIONI, MARGHERITA (Primo)
DI BIASE, ERIKA (Secondo)
CHIRICOZZI, ELENA (Penultimo)
SONNINO, SANDRO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||lug-2018|
|Appare nelle tipologie:||01 - Articolo su periodico|