Researchers link metal ions to neurodegenerative disease

A multi-institutional team of researchers led by Emory University has defined for the first time how metal ions bind to amyloid fibrils in the brain in a way that appears toxic to neurons. Amyloid fibrils are linked to the development of neurodegenerative diseases such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob. Although metal ions, most notably copper, can bind to amyloid in several specific ways, the researchers found that only one way appears toxic.

The findings will appear in the Proceedings of the National Academy of Sciences, Early Edition online during the week of Aug. 6-10 and in the Aug. 14 print edition.

Copper ions, atoms that have acquired an electric charge by gaining or losing one or more electrons, are found naturally in the brain, as are other ions such as zinc and iron. Increasing evidence now links these naturally occurring ions to amyloid assembly and to Alzheimer's disease, says David Lynn, PhD, Emory professor and chair of chemistry and principal investigator of the study.

While little is known about the exact mechanisms governing the formation of amyloid fibrils, the study's results suggest that the exact way amyloid binds to copper ions affects the fibers' architecture, rate of propagation and their effect, if any, on surrounding neurons.

"Not all amyloid fibrils are toxic," says Dr. Lynn. "Amyloid is made of proteins and proteins normally fold into beautiful structures. However, for whatever reason, some misfold and the resulting misfolded structures are also beautiful, but sticky. They stick to themselves and then propagate to form fibrils, but only some of the fibrils turn out to be toxic."

Those who suffer from Alzheimer's disease, for example, have an unusual amount of sticky amyloid fibrils in their brains. Over time, the fibrils accumulate instead of decomposing and increasingly interfere with the brain's structure and function. In contrast, normally folded proteins are clear

Contact: Holly Korschun
Emory University

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