Forgotten Gangliosides: O-Acetylated and Lactone Gangliosides

-acetyl-sialic acid or a sialic acid forming a lactone ring, classified as alkali-labile gangliosides (ALGs), were the focus of extensive research until the late 1990s. Their identification and isolation for structural characterization require strict avoidance of alkaline treatments, a common step in standard ganglioside purification protocols used to eliminate glycerophospholipid contamination. After 2000, scientific interest in alkali-labile gangliosides declined significantly, resulting in a dearth of new information and few updates on their biological significance. However, in recent years, new insights have emerged regarding the potential of anti-acetylated ganglioside antibodies for specific tumor treatments and how ganglioside structures can modulate the activity of membrane receptors through specific interactions. Further knowledge of alkali-labile gangliosides could be very useful for better understanding their significance in both normal and tumor cells. In this manuscript, we intend to revisit the existing knowledge on alkali-labile gangliosides and form hypotheses regarding their possible roles in cells.