In 2006 an estimated 26.6 million people worldwide had Alzheimer's disease and those numbers are expected to have quadrupled by the year 2050. Now scientists in the US have developed a probe to better understand protein aggregation processes linked to the disease.

Songi Han at the University of California, Santa Barbara, and co-workers made the nitroxide-based molecule, which can be attached to specific amino acid sites in a protein. 

The tau hypothesis proposes that tangles of tau proteins lead to Alzheimer's disease © National Institutes of Health (NIH)

Tangles of tau proteins, proteins which are abundant in neurons, are thought by many to give rise to Alzheimer's disease. Han and her colleagues attached their probe to a tau protein at position 322, which sees only moving water molecules within 5 Angstroms. The probe can be used to measure the water's local diffusion coefficient on the surface of a protein as the interaction between the unpaired electron of the probe's nitroxide group and a proton in water increases the probe's nuclear magnetic resonance signal. This allows the researchers to measure water surface dynamics at low concentration, making it a very sensitive tool. 

Han's team used the probe to follow tau protein aggregation on the molecular level. As Han explains, 'being able to measure interfacial and surface hydration dynamics provides us with a unique tool to map out interactions between species or the transport of protons and water across membranes.' Introducing the probe into amyloid fibre proteins, such as those formed by tangled tau proteins, could give a clearer picture of how the fibres form and lead to further insight into the proteins' structural characteristics. 

Mark Wilson, an expert in protein aggregation, University of Wollongong, Australia agrees that 'the approach could offer structural insights into those parts of a protein directly involved in inter-protein binding events underpinning aggregation.' Han adds that understanding protein function in this way is 'key to understanding the building blocks and machinery of life, or the mechanism of failure.'

Paul Cooper

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