GM2A Human

The GM2 Ganglioside Activator (GM2A) is a lipid transfer protein that plays a crucial role in the metabolism of gangliosides, which are glycosphingolipids found in the cell membranes of neurons. GM2A is essential for the degradation of GM2 gangliosides, a process that is vital for normal cellular function and neurological health.

GM2A is a small, soluble protein that binds to GM2 gangliosides and presents them to the enzyme beta-hexosaminidase A (Hex A) for hydrolysis. This interaction facilitates the removal of N-acetyl-D-galactosamine from GM2, converting it into GM3 ganglioside . The proper functioning of this pathway is critical for the prevention of lysosomal storage disorders.

Mutations in the GM2A gene can lead to a rare lysosomal storage disorder known as GM2 gangliosidosis, AB variant . This condition is characterized by the accumulation of GM2 gangliosides in the lysosomes, leading to progressive neurodegeneration. The AB variant is one of three types of GM2 gangliosidosis, the other two being Tay-Sachs disease and Sandhoff disease .

The accumulation of GM2 gangliosides due to GM2A deficiency results in severe neurological symptoms, including motor dysfunction, cognitive decline, and early death . Research has shown that elevated levels of GM2A in the brain are associated with reduced neurite integrity and spontaneous neuronal activity, which are critical factors in neurodegenerative diseases such as Alzheimer’s .

Human recombinant GM2A has been developed to study its potential therapeutic applications. By providing a functional copy of the protein, researchers aim to restore the normal degradation pathway of GM2 gangliosides and alleviate the symptoms of GM2 gangliosidosis. This approach holds promise for the development of treatments for other lysosomal storage disorders as well.