High Copper Exposure May Promote Disease-driving Protein Clumping
Exposure to high concentrations of copper accelerates the formation of toxic clumps of the alpha-synuclein protein — a hallmark of Parkinson’s disease, a study shows.
The study, “Single-Particle Resolution of Copper-Associated Annular α‑Synuclein Oligomers Reveals Potential Therapeutic Targets of Neurodegeneration,” was published in the journal ACS Chemical Neuroscience.
Alpha-synuclein, a protein found abundant in the brain, is thought to help regulate nerve cell function and communication. Toxic buildup of alpha-synuclein clumps (oligomers) is one of the main causes of nerve cell loss in Parkinson’s disease.
Prior research has shown that alpha-synuclein oligomers from Parkinson’s patients have elevated levels of metals. One study found particularly high levels of copper in patients’ cerebrospinal fluid (the fluid that surrounds the brain and spinal cord).
Metal ions can help stabilize the interaction between proteins facilitating their aggregation. Common sources of environmental copper exposure include pesticides, copper-contaminated water, or uncoated copper cookware.
Now, a team led by researchers at the University of Limerick, Ireland, and The Swiss Federal Laboratories for Materials Science and Technology assessed whether exposure to copper can promote the formation of alpha-synuclein oligomers.
To answer this, they first produced their own alpha-synuclein which was maintained in a water solution. To visualize the clumping of the alpha-synuclein at a nanoscale — a nanometer is one billionth of a meter — they employed a technique called atomic force microscopy and Raman spectroscopy. This method involves shining specific wavelengths of light at the sample, and measuring how it reacts.
They observed the lab-made alpha-synuclein protein for 10 days and saw that the oligomers of alpha-synuclein began to form only after five days under their controlled conditions. However, when they added copper ions to the solution, alpha-synuclein oligomers, which formed ring-shaped structures, began to form within a few hours.
“High doses of copper seem to accelerate the aggregation process,” Peter Nirmalraj, PhD, one of the study’s lead author, said in a press release.
The researchers then conducted computer simulations to assess the formation of the ring oligomers in tiny steps of 10 to 100 nanoseconds. The results confirmed that the oligomer rings are formed at early stages of protein transformation.
Overall, the findings add to previous evidence on the potential risk of exposure to certain environmental factors that may lead to diseases like Parkinson’s.
Moreover, the team believes that imaging techniques that can detect these oligomers may help identify and diagnose patients at early stages of the disease using a small sample of cerebrospinal fluid.