Keeping harmful protein fibers at bay

Misfolded clothes, are the bane of many a fashion retail worker’s existence; misfolded proteins on the other hand are not just useless,  they can also be toxic. When proteins in the human body get out of alignment they form linear aggregates known as amyloid fibers that can lead to disorders such as Alzheimer’s and Parkinson’s diseases.

So SRxA’s Word on Health was interested to learn that US researchers have discovered a protein machinery that inhibits the formation and helps to dissolve such fibers.

The researchers set out to study whether two small heat shock proteins (HSPs) – proteins that assist other proteins in folding – could affect the generation of amyloid fibres by a misfolded protein of the same organism (Sup35). Using purified proteins, derived from baker’s yeast they showed that Hsp26 and Hsp42 inhibited amyloid formation.

Even cleverer still, they were able to determine exactly which steps of the process were affected. Hsp42 slowed down early structural reorganization of small aggregates before the fibers were formed, whereas Hsp26 inhibited fiber growth.

All of which, we’re sure you’re saying, is great news for baker’s yeast, but you’ve never seen a loaf of bread with Alzheimer’s!

And here’s the problem.   Humans and other animals lack the yeast enzyme – Hsp104 – that rapidly dissolves amyloid.  As such, it was unclear if and how our cells could get rid of amyloid fibres.

Undeterred, the scientists started to experiment further.  They showed that Sup35 fibers can be dissolved by a combination of several yeast HSPs (Hsp40, Hsp70 and Hsp110) in the absence of Hsp104.  And, the effect was even better if the fibers were pretreated with Hsp26 and Hsp42.

What’s more, they obtained similar results when using the equivalent human HSPs to disaggregate the amyloid fibres involved in Parkinson’s disease. Although amyloid disassembly took many days, the researchers propose that such system could work in long-lasting cells such as neurons.

The full results are published here.

While their findings suggest that enhancing the activity of certain HSPs in affected cells and/or introducing yeast Hsp104 could help to dissolve the amyloid in disorders such as Parkinson’s disease, additional research would be needed to assess the efficacy and safety of such treatments before human testing can begin.

Nevertheless it’s a step in the right direction.  Now, if only we could find an answer to misfolded clothes!

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