Copper exposure in the environment and the protein alpha-synuclein in the human brain could play an important role in the pathogenesis of Parkinson’s disease. Researchers were able to show how the protein takes on an unusual shape when exposed to large amounts of copper ions. The findings could help develop new strategies for the treatment of neurodegenerative diseases.
Long before the onset of the typical muscle tremor, the appearance of defective proteins in the brain could be the first sign. In doing so, they were also able to visualise at the nanoscale the connection with environmental pollution by copper. In addition, the findings could provide opportunities to improve early detection and therapy of the disease.
What is known about Parkinson’s disease is that neurons in the brain die, resulting in a deficiency of the neurotransmitter dopamine. In the later stages of the disease, this leads to muscle tremors, muscle rigidity, and even immobility. The slowly progressive disease is the second most common neurodegenerative disease in the world after Alzheimer’s disease. Environmental factors such as pesticides or metals could promote the occurrence of Parkinson’s. The team led by Empa researcher Peter Nirmalraj from the Transport at Nanoscale Interfaces lab is investigating this hypothesis using imaging techniques and chemical spectroscopy as well as, in collaboration with the team of Damien Thompson at the University of Limerick, computer simulations. The researchers are targeting a protein that is involved in several molecular processes in the development of Parkinson’s: alpha-synuclein. In affected individuals, this endogenous protein clumps together and causes nerve cells to die.
Empa researcher Silvia Campioni from the Cellulose & Wood Materials lab created the protein artificially to visualise the clumping of alpha-synuclein at the nanometer scale.
Using atomic force microscopy, the researchers were then able to observe the protein, which was initially in solution, for ten days as it formed individual insoluble filamentous structures before finally clumping together to form a dense network of fibrils.
The transformation of the soluble protein into clumped fibers about 1 micrometer in length, as they occur during the progression of the disease, can be observed with impressive precision in the laboratory. If the researchers then added copper ions to the protein solution, completely different structures appeared under the microscope: Ring-shaped protein structures about 7 nanometers in size, so-called oligomers, appeared in the test tube within only a few hours.
The existence of such ring-shaped oligomers and their cell-damaging effect is already known. What’s more, the longer fiber-like structures appeared earlier than in a copper-free solu
