Forty years ago, due to the fact that some people with Alzheimer’s disease had aluminum deposits in their brains, scientists began to explore a possible link between overexposure to metals and Alzheimer’s disease. However, after many years of study, no conclusive evidence was able to link aluminum exposure to neurodegenerative diseases, which left researchers to focus on other metals, such as zinc, iron and copper.
Research conducted through Emery University and the University of Georgia has been able show toxic harm done to brain neurons from metal ions binding to amyloid fibrils. Amyloid fibrils are linked to the development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Found naturally in the brain, Copper, zinc and iron ions are atoms that have acquired an electrical charge by gaining or losing one or more electrons. Increasing evidence now links these naturally occurring ions in the brain to amyloid assembly and to Alzheimer’s disease, says David Lynn, Emory chair of chemistry and principal investigator of the study.
Although metal ions, most notably copper, can bind to amyloid in several specific ways, the researchers found that only one way appears toxic. Amyloids are typically hard, waxy deposits consisting primarily of protein found in body tissue. The findings appear in the Proceedings of the National Academy of Sciences.
Although little is known as to how amyloid fibrils are formed, the study’s results suggest that the exact way amyloid binds to copper ions affects the structure of the fibers, the rate in which they multiply, and any effect they may have on surrounding neurons.
“Not all amyloid fibrils are toxic,” says 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.”
An unusual amount of sticky amyloid fibrils have been found in patients who suffer from Alzheimer’s disease. Over a period of time, instead of decomposing shortly after they are produced, as normally folded proteins do, the fibrils accumulate and increasingly interfere with the brain’s structure and function.
By determining only an individual unit of amino acid’s physical and chemical properties when binding with metal, the scientists were able to determine the effect on brain cells according to the activity influencing the assembly and the toxicity of whole amyloid fibrils.
“We showed that the activity of this minimal unit actually replicates the activity of the whole fibril on the neuronal cell. And it does so by binding the metal in a specific way,” says Lynn. They also found that several distinct types of structures could be assembled from individual units of amino acids. “We found that we could build lots of different types of structures with an individual unit: fettuccine-shaped structures, tubes, vesicles, and so on, not just fibers. And this is remarkable,” says Lynn.
“Our findings now lead us to ask what other types of structures these individual units can make, what exactly happens when the units bind to one another, and whether these individual units are important to neurodegenerative diseases or whether the entire fibril must be involved,” says Lynn.
“Like many scientific findings, we know about amyloid because of the diseases it’s associated with rather than because of its benefits,” says Lynn. “However, researchers are also finding situations in which amyloid is beneficial, such as in long-term memory and synapse maintenance in the marine snail.”
From the Desk of Ron White
Sources:
Wikipedia — Neurodegeneration: http://en.wikipedia.org/wiki/Neurodegeneration
Center for Neurodegenerative Disease — Emery-led Study links Alzheimer’s to Lead: http://www.emory.edu/news/Releases/Metals_to_Alzheimers1186774207.html
Proceedings of the National Academy of Sciences, Early Edition online during the week of Aug. 6-10, and in the print edition Aug. 14, 2007
Comments are closed.