Page 1 of 1

Question about research topic: beta-Amyloid unfolding

Posted: Mon Mar 16, 2009 6:52 am
by old_fool
Is anyone using the F@H resources in beta-Amyloid folding/unfolding?

How about research on cytokines, TNF-alpha receptors etc.? I trust that you guys know why I am asking these: I have a very close person suffering from early onset AD. It's devastating for him. Knowing that maybe some of my WUs go towards research in those fields, would make me feel better, it would give more meaning to my efforts.


Note to mods: feel free to move this thread to a different subforum, if you think a more appropriate one exists.

Re: Question about research topic: beta-Amyloid unfolding

Posted: Tue Mar 17, 2009 9:27 pm
by Kim Branson
Hi,

We actually have 2 current research projects in the areas you mention. We have had a project on new compounds to inhibit Abeta aggregation (these compounds are designed to mimic regions of abeta identified from Abeta aggregation simulations running on folding@home).

In addition we have been developing a new code to design inhibitors of protein-protein interaction. I have a particular interest in the design of inhibitors of cytokine signalling (having previously worked on small molecule inhibitors of IL-6 ternary complex assembly). We hope to have this new core "Ocker" in a beta testing "real soon now".

The mutations in early onset alzheimers tend to be either in the Abeta peptide (produced from the processing of the APP protein itself) or in the presenilins themselves. If your relative/close person has the type of early onset due to Abeta mutations you can take some solace in knowing this work is directly aligned. There is some excellent new work on modulation of the processing pathways from various pharmaceutical companies as well.

Alzheimers is a complex multifactorial disease and many approaches may be beneficial. We are currently interested in the design of small molecule inhibitors for protein-protein interaction (particularly Abeta) but there are other therapeutics approaches using antibodies in trial. These currently rely on a passive immunisation approach due to the side effects from the active immunisation trials.

There are also some therapeutic approaches involving the chelation of metals, but for reasons related to the disease pathogenesis these would most likely not be applicable to your relative.

cheers

Kim

Re: Question about research topic: beta-Amyloid unfolding

Posted: Tue Mar 17, 2009 9:59 pm
by old_fool
Kim,

thank you very much for answering my post, which I thought will be unnoticed.

After a first reading, I only understood half of it, but with regards to the beta Amyloid research you mention, it's puzzling how the Amyolid plaques were found also in persons who had no symptoms of AD whatsoever. My very naive understanding of biochemistry makes me believe that a lateral thinker should have a good look at this fact.

Due to the rapid progress of early onset AD, your noble effort (and that of many other scientists involved also in trials right now) may not yield results fast enough for my beloved friend. The only grace is the onset of apathy - and the cessation of emotional pain and fear that this condition brings him. I'd much rather hope in a miraculous new scientific breakthrough.

In any case, you have definitely motivated me to dedicate even more resources to F@H. As I said, it gives more meaning to the effort when it gets personal like this.

As for a motivation for you (if you even needed one): know that AD, especially for a young person looking forward to his productive life (also in research BTW.) and marriage, is a very scary, traumatizing everyday experience. Seeing him forget words, names, events from his own life - and seeing how he is aware of his situation and agonizing over it, I believe his words "living hell". Sudden death seems so much more merciful.

Thank you again for your post. I'll share it with my friend.


m



Kim Branson wrote:Hi,

We actually have 2 current research projects in the areas you mention. We have had a project on new compounds to inhibit Abeta aggregation (these compounds are designed to mimic regions of abeta identified from Abeta aggregation simulations running on folding@home).

In addition we have been developing a new code to design inhibitors of protein-protein interaction. I have a particular interest in the design of inhibitors of cytokine signalling (having previously worked on small molecule inhibitors of IL-6 ternary complex assembly). We hope to have this new core "Ocker" in a beta testing "real soon now".

The mutations in early onset alzheimers tend to be either in the Abeta peptide (produced from the processing of the APP protein itself) or in the presenilins themselves. If your relative/close person has the type of early onset due to Abeta mutations you can take some solace in knowing this work is directly aligned. There is some excellent new work on modulation of the processing pathways from various pharmaceutical companies as well.

Alzheimers is a complex multifactorial disease and many approaches may be beneficial. We are currently interested in the design of small molecule inhibitors for protein-protein interaction (particularly Abeta) but there are other therapeutics approaches using antibodies in trial. These currently rely on a passive immunisation approach due to the side effects from the active immunisation trials.

There are also some therapeutic approaches involving the chelation of metals, but for reasons related to the disease pathogenesis these would most likely not be applicable to your relative.

cheers

Kim

Re: Question about research topic: beta-Amyloid unfolding

Posted: Tue May 19, 2009 4:29 pm
by AndreyVoronkov
Kim, I am very interested in molecular dynamics studies of amyloid beta in complex with different proteins and ligands. Is it possible to find somewhere your results in this field? I can't find any papers on Science page, but Alzhemer's disease is mentioned several times in the description of the project - so I decided to ask you about it.

Re: Question about research topic: beta-Amyloid unfolding

Posted: Tue May 19, 2009 9:38 pm
by VijayPande
There's a lot of results to come, but the first one has come out (see our Results page on our web site).