Protein Involvement On Metal Homeostasis May Hold Implications In Alzheimer’s Disease

Protein Involvement On Metal Homeostasis May Hold Implications In Alzheimer’s Disease

In a recent study published in Angewandte Chemie, a team of researchers from the University of Melbourne have identified that a specific protein known for its involvement in the progression of Alzheimer’s disease (AD) has properties that could be beneficial for human health. The study findings may help scientists to improve their understanding on the complexity of brain chemistry behind the development of Alzheimer’s disease.

In the study titled “A Functional Role for Aβ in Metal Homeostasis? N-Truncation and High-Affinity Copper Binding”, an international team of scientists, led by Dr Simon Drew at the University of Melbourne and Prof Wojciech Bal at the Polish Academy of Sciences, the team showed that a shorter form of the beta amyloid protein works as a sponge to bind a metal that when in excess can harm brain tissue.

Scientists have gained interest in studying the role of beta-amyloid as a precursor in the development of AD, especially because clumps of the protein are formed in brains of people suffering from the condition.

Two decades ago, high levels of copper were noticed within these clumps. Copper is fundamental to health, however high levels can produce damaging free radicals. Researchers started to question if this copper might be a precursor of AD and discovered that beta-amyloid could bind to the metal and prevent it from producing these harmful free radicals.

“This short form has been overlooked by most researchers since the composition of beta amyloid was first identified 30 years ago,” Dr. Simon Drew explained. “We know that the shorter form of beta amyloid is present in the diseased brain, but we now know that it is abundant in healthy brains as well. The small change in length makes a huge difference to its copper binding properties. We found that the short form of the protein is capable of binding copper at least 1000 times stronger than the longer forms.  It also wraps around the metal in a way that prevents it from producing free radicals”.

“Given these properties and its relative abundance, we can speculate this type of beta amyloid is protective. It’s very different from the current view of how beta amyloid interacts with biological copper”, he added.

Currently, treatments to lower beta amyloid production have presented only a modest ability to slow down the decline in cognition. The team is now developing a strategy to identify the copper-bound form of the short beta amyloid protein within the body, which will enable researchers to evaluate not only the amount of copper existent in the brain but also if it safely leads copper from one place to another, and how this may change throughout ageing and disease progression.

“If a beneficial role in copper balance can be established, it’s still possible to have too much of a good thing,” Dr. Drew said. “As the amount of beta amyloid in the brain increases during Alzheimer’s disease, the shorter form can also clump together and this may interfere with its normal function.  Higher levels of the short form may further enable it to soak up copper from other places where it is needed. It could be a Jekyll and Hyde scenario.”

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