Scientists at the National Institutes of Health (NIH) have discovered that an important cellular quality control mechanism may actually be toxic to some brain cells during prion infection. The research, published by Cell Press in the Sept. 16th issue of the journal Developmental Cell, proposes a new general mechanism of cellular dysfunction that can contribute to the devastating and widespread neuronal death characteristic of slowly progressing neurodegenerative diseases.
Prions cause a number of untreatable and fatal neurodegenerative disorders, including bovine spongiform encephalopathy ("mad cow disease") in cattle and Creutzfeldt-Jakob disease in humans. "We know that abnormal metabolism of a normal prion protein (PrP) is at the root of these diseases. However, the pathways that lead to selective neuronal death are unknown," explains senior author Dr. Ramanujan S. Hegde from the National Institute of Child Health and Human Development in Bethesda, Maryland.
The endoplasmic reticulum (ER) is a membrane-bound subcompartment of the cell that helps fold newly-made proteins and route them to their final destinations within or outside the cell. When protein folding or trafficking is temporarily compromised, the ER experiences "stress" and compensates using a specific ER stress response.
