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Know your enemy
Date:4/25/2014

is very well defined and a larger one that is virtually a chain composed of the smaller ones. The oligomers are thus capable of linking up in the same way as the fibrils, but in chains that inhibit the fibrils. "You could say that they put a spanner in the works regarding the formation of fibrils," says Professor Otzen. It could possibly be a help to shift the focus even further away from the fibrils, which are formed in a different process than the oligomers, and which should not be a target for pharmaceutical products on their own.

Description of the enemy

So what does our adversary look like? The researchers can now help provide us with a better answer. An oligomer consists of a very stable interior and a more diffuse sphere surrounding it, where the protein is not as compact and where it flaps around a little

And yet the image is even more complicated than that! Because if you take a closer look at the little oligomer, there are also two types here. To study this, the researchers used very advanced mass spectrometric techniques carried out together by Associate Professor Thomas Jrgensen and PhD student Simon Mysling at SDU. Associate Professor Jrgensen's group consists of world experts in hydrogen-deuterium exchange (HDX), which can be used to study how flexible or loosely structured the different parts of a protein are. It turns out that two different oligomers with different degrees of flexibility can be present at the same time. One type admittedly 'flaps around' more than the other, but it is nevertheless very stable and does not turn into fibrils because it is unable to 'absorb' monomer proteins and thereby grow bigger. This oligomer simply clumps together to form larger oligomers, and is the dominating (and toxic) type, corresponding to the structure shown above. The other type (which only accounts for 10󈞀% of the total oligomer population) is capable of absorbing monomers and becoming (harmless) fibrils.

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Contact: Daniel Otzen
dao@inano.au.dk
45-20-72-52-38
Aarhus University
Source:Eurekalert

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