Proteins called chaperones bind to damaged or defective proteins in cells of the body. The chaperones ferry their cargo to the cells’ lysosomes, which digest and recycle waste material. To successfully get their cargo into lysosomes, however, chaperones must first “dock” the material onto a protein receptor called LAMP2A that sprouts from the membranes of lysosomes. The more LAMP2A receptors on lysosomes, the greater the level of CMA activity possible.
The team developed a novel drug that shows potential for treating Alzheimer’s. The new drug, called CA, works by increasing the number of those LAMP2A receptors. “CA (experimental drug) restores LAMP2A to youthful levels (in mice), enabling CMA to get rid of tau and other defective proteins so they can’t form those toxic protein clumps,” said Cuervo.