One of the hallmarks of Alzheimer’s disease is the abnormal clumping of beta-amyloid proteins in the brain, resulting in the death of brain cells. The discovery that small heat shock proteins prevent uncontrolled protein clumping has opened the possibility of developing drugs that emulate this effect. Now, a new study takes this a step further by revealing how small heat shock proteins interact with beta-amyloid to prevent clumping.

Share on Pinterest These electron microscope images show beta-amyloid in the absence (left) and presence (right) of alphaB-crystallin.

Image credit: Andi Mainz/TUM

The researchers, from the Technical University of Munich (TUM) and the Helmholtz Zentrum München, both in Germany, report their findings in the journal Nature Structural & Molecular Biology.

Small heat shock proteins are “helper” or “chaperone” proteins that perform a variety of roles, including the guarding of other proteins during times of stress to stop them becoming abnormal, such as folding into the wrong shape or clumping when they should not.

One reason to understand these helper proteins is the hope of using them as agents in the treatment of brain-wasting diseases such as Alzheimer’s. Small heat shock proteins attach themselves to the deformed proteins before they start to aggregate and keep them in a soluble state – thus preventing the clumping.

In the case of Alzheimer’s disease, the heat shock protein that stops beta-amyloid aggregating to form long fibrils that clog up brain cells is called alpha-B-crystallin. Other heat shock proteins are associated with neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis.