Copper leads to protein aggregation and may cause Parkinson’s disease: Study

Copper exposure in the environment, as well as the protein alpha-synuclein in the human brain, may have a role in the pathophysiology of Parkinson’s disease. The protein takes on an odd structure when exposed to huge levels of copper ions, according to the researchers. The discoveries might aid in the development of novel treatments for neurological illnesses.
The causes of Parkinson’s disease are yet unknown.

The presence of faulty proteins in the brain might be the first clue long before the beginning of typical muscular tremors. Empa and the University of Limerick in Ireland have now examined the anomalous structure of these alpha-synucleins in the form of protein rings.

They were also able to observe at the nanoscale the link between copper contamination and environmental pollution. This elucidates the progression of neurodegenerative illness and the function of biometals in the disease process. Furthermore, the discoveries might pave the way for better illness identification and treatment.

Parkinson’s disease is defined by the death of neurons in the brain, resulting in a lack of the neurotransmitter dopamine. This causes muscular tremors, stiffness, and even immobility in the latter stages of the disease. After Alzheimer’s disease, the slowly progressing condition is the world’s second most prevalent neurological disease.

Environmental factors such as pesticides or heavy metals may contribute to the development of Parkinson’s disease.

The Transport at Nanoscale Interfaces group, directed by Empa researcher Peter Nirmalraj, is examining this idea using imaging methods and chemical spectroscopy, as well as computer simulations in partnership with Damien Thompson’s team at the University of Limerick. The researchers are focusing on alpha-synuclein, a protein that is implicated in multiple molecular stages in the development of Parkinson’s disease.

This endogenous protein clumps together in afflicted individuals, causing nerve cells to perish. Copper in high amounts, according to the study, interferes with these mechanisms and speeds up the illness process.

Empa researcher Silvia Campioni from the Cellulose & Wood Materials team created the protein artificially to visualise the clumping of alpha-synuclein at the nanoscale scale. The researchers used atomic force microscopy to see the protein, which was originally in solution, produce individual insoluble filamentous structures before clumping together to create a dense network of fibrils over a ten-day period. The change of the soluble protein into clumped fibres around 1 micrometre in length, as seen in the photos, can be seen in the laboratory with astonishing precision during the evolution of the disease.

When the researchers introduced copper ions to the protein solution, they saw radically different shapes beneath the microscope: Within a few hours, ring-shaped protein structures around 7 nanometers in size, known as oligomers, emerged in the test tube. The presence of such ring-shaped oligomers, as well as their cell-damaging action, is well documented. Furthermore, in a copper-free solution, the longer fiber-like structures formed early.

“High amounts of copper appear to hasten the aggregation process,” says Peter Nirmalraj. Furthermore, under the effect of copper, this peculiar ring-shaped protein structure forms quite fast, presumably indicating the start of the disease process or even initiating it.

The researchers also used molecular dynamics computer simulations in small increments of 10 to 100 nanoseconds to study the binding of copper ions to alpha-synuclein.

Because oligomer rings emerge at the start of protein transformation, Nirmalraj believes they might be utilised as a target for new types of therapy. Furthermore, the findings might aid in the creation of a Parkinson’s test that can detect the illness at an early stage in bodily fluids, such as spinal fluid samples.