Cytoprotective effects of liposomal ganglioside GM1

Gangliosides, glycosphingolipids with one or more N-acetyl-neuraminic acid groups, play essential roles in various cellular and biological processes, among them are cell signaling, neuronal development, cell-cell recognition and the modulation of immune response. Based on their multiple biological roles, the pharmacological utilization of gangliosides for the therapy of several clinical conditions is currently widely being explored but hampered by its limited water solubility. To increase the bioavailability of poorly water-soluble therapeutic agents, pharmaceutical nanocarriers such as liposomes have been developed over the last fifty years. Ganglioside GM1 incorporated into liposomes was proposed during the 1980s for rendering them long-circulating following their intravenous administration, but GM1 was soon replaced by polyethylene glycol which gave rise to the concept of Stealth Liposomes. More recently, the ability of exogenous GM1 to ameliorate oxidative stress was revealed, leading us to investigate the cytoprotective effect of liposomal GM1 under a variety of pathological conditions. Here we review all data showing the antioxidant effect of exogeneous GM1 and based on literature findings and our own, we propose a mechanism by which liposomal exogenous GM1 is able to trigger the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which is a critical cellular defense mechanism protecting against oxidative stress and other types of cellular damage.