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Inflammation and specific gene mutations implicated in Parkinson's disease

19 October 2020
Appeared in BioNews 1068

A link between inflammation and specific genetic mutations in Parkinson's patients has been established according to a new study.

Scientists identified two potential biomarkers – interleukin 6 (IL6) and circulating mitochondrial DNA – that could help to better understand the basis of the disease and monitor its progression in patients. The researchers also suggest that anti-inflammatory drugs might be useful in treating Parkinson's disease.

'Our study suggests that treatment with anti-inflammatory drugs holds the potential to alleviate the course of Parkinson's disease – at least for patients with mutations in the Parkin or PINK1 gene,' said Dr Anne Grünewald, head of the molecular and functional neurobiology group at the Luxembourg Centre for Systems Biology at the University of Luxembourg, and co-lead author of the study.

Parkinson's disease is a late-onset neurological disease and though the majority of cases occur in patients with no family history of the disease, around 15 percent of cases are linked to genetic factors. The most common of these genetically-linked cases have mutations in the genes Parkin or PINK1. This study aimed to untangle the molecular basis of the disease in this subset of patients.

Published in the journal Brain, the study looked at 245 patients with Parkinson's disease and showed that patients carrying mutations in the Parkin or PINK1 genes have an increased level of circulating mitochondrial DNA and IL6 compared to patients without these mutations.

The researchers proposed that this is because mitochondrial damage caused by Parkin and PINK1 mutations leads to release of mitochondrial DNA and an inflammatory response in these patients. Parkin and PINK1 are usually involved in the clean-up of damaged mitochondria, so mutations in these genes can result in damaged parts of mitochondria, including mitochondrial DNA, being released. When this happens, the immune system recognises this DNA as out of place and tries to clean it up by initiating an inflammatory response, and increased IL6 levels. When IL6 reaches the brain, it is thought to play a role in neurodegeneration.

The researchers found that, compared to healthy controls, the levels of IL6 were not only increased in patients with Parkin and PINK1 mutations on both chromosomes (homozygous), but also in patients with the mutation on just one chromosome (heterozygous).

'This tells us that heterozygous mutations also constitute a strong risk factor for the onset of Parkinson's disease. Even before the disease has broken out in these heterozygous carriers, we might be able to detect it at an early stage by monitoring IL6 in the serum.' said Dr Grünewald. 'Our findings have a high value for potential clinical applications, be it biomarkers in the patient's serum that detect the state of the disease or new therapeutic approaches targeting the innate immune response in Parkin/PINK1-associated Parkinson's disease.'

SOURCES & REFERENCES
Mitochondrial damage-associated inflammation highlights biomarkers in PRKN/PINK1 parkinsonism
Brain |  8 October 2020
New study highlights links between inflammation and Parkinson's disease
University of Luxembourg |  8 October 2020
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