The disease, called GM1 gangliosidosis, disrupts the normal function of brain cells and causes them to self-destruct. The St. Jude discovery offers strong evidence for the cause of GM1 gangliosidosis in children. GM1 gangliosidosis is a lysosomal storage disorders, an inherited disease in which one or more enzymes in the lysosomes are defective. Lysosomes are the cell's recycling centers, where proteins, fats and other molecules are broken down into their basic building blocks, which are then reused to make new molecules.
Lysosomal storage diseases occur when lysosomes lack the enzymes they need to perform their recycling tasks, leading to abnormal accumulation of the molecules the lysosome is supposed to break down. These diseases are responsible for most severe cases of nerve degeneration and mental retardation among children.
The discovery identifies for the first time the endoplasmic reticulum (ER), the cell's protein processing factory as the location of biochemical reactions leading to brain cell death in children with this disease.
"Our finding is exciting because children with GM1 gangliosidosis are severely affected and their outlooks are dismal," said Alessandra d'Azzo, Ph.D., member of the St. Jude department of Genetics and Tumor Cell Biology. "Now that we have a better understanding of what causes the damage, we may be able to design treatments that specifically remedy this problem. If this finding holds true for other lysosomal storage diseases, the impact could be especially fruitful."
d'Azzo is senior author of the Molecular Cell report.