A new study sheds light on the biological processes through which exposure to some metals can contribute to the onset of Parkinson’s-like symptoms.
The study focuses on the metal manganese, which has a range of industrial uses as an alloy. Anumantha Kanthasamy, a professor in veterinary medicine and chair of neurotoxicology at Iowa State University, says the research details how manganese exposure can lead to misfolded proteins in the brain, which cause a neurological disease.
The findings could lead to earlier detection of Parkinson’s disease and better outcomes for patients, Kanthasamy says.
Small amounts of manganese are necessary for the proper functioning of the human body, but studies have linked too much exposure with neurological symptoms much like those patients with Parkinson’s disease experience, he says.
Researchers have noted links between manganese and neurological disorders since the 1950s, Kanthasamy says, because of the tendency of manganese to accumulate in brain tissues.
Disease progression
Manganese combines with a protein in the brain called alpha- synuclein, according to the new study. Previous studies showed the protein was susceptible to misfolding, but Kanthasamy and colleagues set out to discover how it interacted with manganese and how that interaction facilitates the progression of disease.
The researchers found the pathological form of misfolded alpha-synuclein proteins package into vesicles, which allow the misfolded proteins to transfer from cell to cell to propagate the protein-seeding activity. These vesicles provoke inflammation of tissues and can lead to a neurodegenerative response, according to the study, which appears in Science Signaling.
The study drew on data gathered from mice as well as welders’ blood serum samples. Welders exposed to manganese had increased misfolded alpha-synuclein serum content, meaning they have a higher risk for developing Parkinson’s symptoms, Kanthasamy says.
Earlier detection
The research could eventually contribute to a new assay, or medical test, to detect the presence of misfolded alpha-synuclein proteins. This could lead to earlier detection of Parkinson’s disease and a way to gauge the effectiveness of drugs designed to slow the disease.
“As the disease advances, it’s harder to slow it down with treatments,” Kanthasamy says. “Earlier detection, perhaps by testing for misfolded alpha-synuclein, can lead to better outcomes for patients. Such a test might also indicate whether someone is at risk before the onset of the disease.”
Kanthasamy cautions the research is still at an experimental stage, meaning it could be years before such an assay could be available.
Clinicians at Penn State provided the welders’ blood serum. Dilshan S. Harischandra, a former member of Kanthasamy’s lab who now works at the University of Pennsylvania, is the study’s lead author. The National Institute of Environmental Health Sciences funded the work.
Source: Iowa State University
