Science News

Alzheimerís prion protein clue

Wed, 25th Feb 2009

More than 20 million people around the world are affected by Alzheimerís disease, a degenerative brain condition that is currently incurable. We know that many of the effects of the disease are due to the buildup of a protein called amyloid-beta, which makes lumps, called plaques, in the brain. 

Human prion protein, residues 125-228, created from protein database (PDB) entry 1QM3.But until now it hasnít been clear exactly how amyloid protein starts to  build up in brain cells, or the root cause of the illness. But this week, scientists in the US have discovered that the buildup of amyloid might be aided by a rogue protein Ė the prion protein.

The prion protein, PrP, is found in many different cells and sits in the membrane that surrounds cells. Normally, it does a useful job helping brain cells to respond to changes in the environment around them, as well as controlling the immune cells in the brain and helping to grow new neurons. But sometimes PrP is found in a different shape, or conformation, and this is where the trouble starts, as it causes severe problems in the brain. Itís high levels of the bad form of PrP that lead to CJD.

Writing in this weekís edition of the journal Nature, the researchers discovered that amyloid-beta can stick to the normal form of the prion protein, and this might be what causes amyloid to build up in brain cells.  Importantly, they discovered that little groups of amyloid are more likely to stick to the prion protein than single amyloid molecules, suggesting that itís important for building up amyloid plaques, and could be a key step in Alzheimerís.

The scientists went on to look at samples of mouse brains, particularly looking at the hippocampus Ė the part of the brain thatís involved in learning and memory, which is badly affected in Alzheimerís.  They found that in brain samples from normal mice, the buildup of amyloid protein blocked a process called long term potentiation Ė which is basically how the brain builds memory. But in samples from mice that lacked the prion protein, amyloid didnít cause problems with long term potentiation. So this shows that the prion protein is a key link in the chain.

This discovery is pretty exciting because it gives us a new angle for Alzheimerís treatments. Perhaps if researchers could develop drugs that block the interaction between amyloid and the prion protein, this might be  potential way to prevent the plaques building up, or reduce their effects on the brain. 

But thereís a lot we donít know. For example, we donít know if the prion protein changes shape once it has stuck to amyloid Ė does it stay in the normal conformation, or change to the bad version? And itís clear that the prion protein isnít the whole story, because if you get rid of the prion proteins altogether, you only reduce the binding of amyloid to brain cells by about 50%. But itís certainly a good start, and an exciting new lead for future research.

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