One mechanism for cleaning up cells involves forming a membrane around the protein or other cellular structure requiring removal. These "garbage bags" (more formally known as autophagosomes) then travel to enzyme-filled sacs known as lysosomes that fuse with the bags and digest their cargo. But the clean-up efforts go awry in Huntington's disease.

Dr. Cuervo and her team found that the defective huntingtin proteins stick to the inner layer of autophagosomes, preventing them from gathering garbage. The result: Autophagosomes arrive empty at the lysosomes; and cellular components that should be recycled instead accumulate, causing toxicity that probably contributes to cell death.

This finding, Dr. Cuervo noted, shows that activating the lysosomes of cells - one of the proposed treatments for Huntington's disease - won't do any good.

"It doesn't matter how active your lysosomes are if they're not going to receive any cellular components to digest," she said. "Instead, we should focus on treatments to help autophagosomes recognize intracellular garbage, perhaps by minimizing their contact with the defective huntingtin protein. By enhancing the clearance of cellular debris, we may be able to keep Huntington's patients free of symptoms for a longer time."

Source: Albert Einstein College of Medicine