They find a mechanism that would reverse Alzheimer’s and Parkinson’s

A recently discovered mechanism that is activated when cells become stressed can open a pathway to help prevent the aggregation of proteins which is commonly seen in neurodegenerative diseases.

An investigation led by the University of Cambridge (United Kingdom) that published “Nature Communications” describes this mechanism, related to cellular stress and protein folding. If it could be activated without disturbing the cells, a way could be found to treat some dementias.

A hallmark of diseases such as Alzheimer’s and Parkinson’s – collectively known as neurodegenerative diseases – is the accumulation of misfolded proteins that form aggregates with the ability to cause irreversible damage to neurons.

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Protein folding is a normal process in the body and, in healthy individuals, cells have a kind of quality control to ensure that those that do it wrong are destroyed, but in neurodegenerative diseases, this system deteriorates, with consequences potentially devastating.

The newly identified mechanism seems to reverse the accumulation of aggregates, but not by completely removing them, but rather by refolding them.

“Just as when we get stressed by a heavy workload, cells can also ‘stress’ if they are asked to produce a large amount of protein,” for example when they produce antibodies in response to an infection, explained Edward Avezov of the University of Cambridge.

The team focused on stressing a component of cells called the endoplasmic reticulum, which performs functions such as synthesizing, folding, modifying and transporting necessary proteins on the surface or outside the cell.

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The initial hypothesis was that stressing the endoplasmic reticulum could lead to protein misfolding and aggregation by decreasing its ability to function properly, but the result they discovered was just the opposite.

By stressing the cell, the aggregates were eliminated and not because they were degraded but because they unraveled, allowing them to fold again correctly.

“If we can find a way to wake up this mechanism without stressing cells – which could do more harm than good – then we might find a way to treat some dementias,” Avezov said.

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

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