'Stressed' cells offer clues to eliminating build-up of toxic proteins in dementia

It's often said that a little stress can be good for you. Now scientists have shown that the same may be true for cells, uncovering a newly-discovered mechanism that might help prevent the build-up of tangles of proteins commonly seen in dementia.

A characteristic of diseases such as Alzheimer's and Parkinson's—collectively known as neurodegenerative diseases—is the build-up of misfolded proteins. These proteins, such as amyloid and tau in Alzheimer's disease, form 'aggregates' that can cause irreversible damage to nerve cells in the brain. Protein folding is a normal process in the body, and in healthy individuals, cells carry out a form of quality control to ensure that proteins are correctly folded and that misfolded proteins are destroyed. But in neurodegenerative diseases, this system becomes impaired, with potentially devastating consequences.

In a study published recently  in Nature Communications, a team of scientists has identified a new mechanism that appears to reverse the build-up of aggregates, not by eliminating them completely, but rather by 'refolding' them.

Just like when we get stressed by a heavy workload, so, too, cells can get 'stressed' if they're called upon to produce a large amount of proteins. There are many reasons why this might be, for example when they are producing antibodies in response to an infection. 

Scientists were surprised to find that stressing the cell actually eliminated the aggregates in this case—not by degrading them or clearing them out, but by unraveling the aggregates, potentially allowing them to refold correctly.

If we can find a way of awakening this mechanism without stressing the cells—which could cause more damage than good—then we might be able to find a way of treating some dementias.

The main component of this mechanism appears to be one of a class of proteins known as heat shock proteins (HSPs), more of which are made when cells are exposed to temperatures above their normal growth temperature, and in response to stress.

 Stress-induced protein disaggregation in the Endoplasmic Reticulum catalysed by BiP., Nature Communications (2022). DOI: 10.1038/s41467-022-30238-2