This abnormal folding, similar to the cycle of neuronal protein misfolding observed in disorders such as Parkinson's and Alzheimer's diseases, leads to brain damage and neurodegenerative disease.
Researchers said their study, published in Science Advances, established a direct link at molecular level, between copper exposure and prion protein neurotoxicity.
Research methods included using a fluorescence-based technique that identified misfolded prion proteins with single-molecule sensitivity and determined the role of metal ions in misfolding.
The researchers used this technique to show that misfolding begins when copper ions bind to the unstructured tail of the prion protein.
They also used a single-molecule atomic force microscopy assay to measure the efficiency of prion protein clumping.
This technique showed them that misfolded prion proteins stick together nearly 900 times more efficiently than properly folded proteins.
Taken together, the results from all the methods used identified the biophysical conditions and mechanisms for copper-induced prion protein misfolding, clumping and neurotoxicity.
Despite the findings, author Professor Sanjeevi Sivasankar of Iowa State University cautioned that the study did not directly address the infectivity of prion diseases.
He said: "There are different strains of misfolded prion proteins and not all of them are pathogenic.
"Although we do not show that the strains generated in our experiments are infectious, we do prove that copper ions trigger misfolding of prion proteins which causes toxicity in nerve cells."
The research groups plan to perform additional studies to determine if the copper-induced misfolding causes disease.
Professor Sivasankar noted that a unique aspect of the project was the integration of biophysical and neurotoxicological research approaches, which has the potential to transform studies of the molecular basis for neurodegenerative diseases.
He said: "This study has major implications to our understanding the role of metals in protein misfolding diseases including prion, Alzheimer's and
Parkinson's diseases."
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http://health.einnews.com/article/333929864/U8Cv_1x3bGixm-fw
http://health.einnews.com/article/333929864/U8Cv_1x3bGixm-fw
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