In healthy cells, a structure called the endoplasmic reticulum (ER) helps make and fold proteins correctly. Unfortunately, this structure is drastically altered during normal aging and in Alzheimer’s, resulting in cells that are less able to repair misfolded and damaged proteins. These misfolded and damaged proteins build up and stress the cells; this leads to nerve cell damage.
Protein-folding is monitored in the ER by a biological process called the unfolded protein response (UPR). This process is activated by proteins on the surface of the ER that act as sensors of misfolded proteins. One of the UPR sensor proteins, (called inositol-requiring enzyme 1 (IRE1)) in turn activates the UPR to help correct folding processes. However, continuous activation of the sensor protein, which may occur during Alzheimer’s, leads to cell death.
PI: Claudia Duran-Aniotz
Support: Alzheimer’s Association