Pharma R&D Today
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Proteins behaving badly
Posted on January 5th, 2016 by Joanna Aldred in Chemistry
The best present I ever received as a child was a game called Mousetrap. For those unlucky enough not to have played this: releasing a lever leads to a series of seemingly random events, such as a boot kicking a ball, and finally to a diver jumping into a bath. This final act may or may not lower a trap on the unsuspecting (plastic) mouse adding an extra element of chance to whether you win or loose.
Elements of cells can have similarly unexpected and seemingly random effects. Take mitochondria, those mysterious organelles that control so much in the body, for example. When mitrochondria start malfunctioning, this may lead to a build-up of proteins in the brain. These proteins, parked in places where they are not wanted and doing no good at all, cause neurodegeneration. This degradation of the brain cells leads to diseases such as Alzheimer’s, Parkinson’s, ALS (amyotrophic lateral sclerosis) and Huntington’s.
Proteins themselves also contribute to mitochondria dysfunction: find a way to make these proteins behave correctly and you can stop the build-up of proteins and other fatal signalling processes that lead to neurodegenerative diseases. A new review in Bioorganic and Medicinal Chemistry Letters looks at the proteins that cause mitochondria to dysfunction.
One of the reasons why there is as yet little progress in this area is because of its complexity. This review describes 12 different proteins divided into 5 categories. Each protein has a different effect on the mitochondria. Deploying small molecule ligands that can modulate behaviour of these proteins can prevent the destructive effects on the mitochondria. Some success has been booked but clinical trials have yet to show much success.
It would be fantastic news if there was a single protein in the mitochondrion that could prevent all neurodegenerative diseases. Since this is not so, there would seem massive scope for further research into these mitochondrial proteins. All that is needed is a very large research budget. Now wouldn’t that be a good present.
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