Excerpt

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.

Autophagy: cellular and molecular mechanisms

weird cell field

Abstract

Autophagy is a self‐degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum and peroxisomes, as well as eliminating intracellular pathogens.

Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to non‐apoptotic cell death. Autophagy can be either non‐selective or selective in the removal of specific organelles, ribosomes and protein aggregates, although the mechanisms regulating aspects of selective autophagy are not fully worked out.

In addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability and prevents necrosis, giving it a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections.

This review summarizes the most up‐to‐date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease.

FULL TEXT: Journal of Pathology