New study highlights links between inflammation and Parkinson's disease


Date:
October 14, 2020
Source:
University of Luxembourg
Summary:
Researchers established an association between inflammation and
specific genetic mutations in Parkinson's patients. The study
highlights two biomarkers that could be used to assess Parkinson's
disease state and progression. The results also suggest that
targeting the immune system with anti-inflammatory medication
holds the potential to influence the disease course, at least in
a subset of patients.



FULL STORY ========================================================================== Around 15% of Parkinson's disease cases are related to a known genetic background, out of which mutations in the Parkin and PINK1 genes are
among the most frequent ones. Thus, revealing cellular mechanisms which
are altered by these mutations is crucial for the development of new therapeutic approaches.

In this study, the researchers analysed the blood serum of 245
participants from two independent cohorts and showed that patients
carrying mutations in the Parkin or PINK1 genes have an increased level
of circulating mitochondrial DNA and interleukin 6 (IL6).


========================================================================== These results indicate that deficiency in Parkin or PINK1 proteins --
caused by a mutation on the corresponding gene -- leads to impaired
mitophagy. This dysfunction at the mitochondria level causes the release
of mitochondrial DNA, thereby triggering inflammation and the elevation
of interleukin 6 levels in the blood. When reaching the brain, IL6 is
then thought to play a role in neurodegeneration. "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," explains Prof.

Anne Gru"newald, head of the Molecular and Functional Neurobiology group
at the LCSB and one of the two senior authors of the study.

By studying the difference between patients carrying the Parkin or PINK1 mutation either on one (heterozygous) or both chromosomes, the researchers
also showed that monitoring the level of systemic inflammation in the
blood might be used as a biomarker for these genetic forms of Parkinson's disease. Whereas patients with mutations in both chromosomes showed
elevated levels of interleukin 6 compared to heterozygous patients,
the latter still displayed a significant increase compared to healthy
controls. "This tells us that heterozygous mutations also constitute
a strong risk factor for the onset of Parkinson's disease," explains
Prof. Gru"newald. "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." Similarly, the study showed that
the level of circulating mitochondrial DNA could serve as a marker of
the progression of the disease for heterozygous Parkin/PINK1 mutation
carriers.

Prof. Gru"newald concludes: "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."

========================================================================== Story Source: Materials provided by University_of_Luxembourg. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Max Borsche, Inke R Ko"nig, Sylvie Delcambre, Simona Petrucci,
Alexander
Balck, Norbert Bru"ggemann, Alexander Zimprich, Kobi Wasner,
Sandro L Pereira, Micol Avenali, Christian Deuschle, Katja
Badanjak, Jenny Ghelfi, Thomas Gasser, Meike Kasten, Philip
Rosenstiel, Katja Lohmann, Kathrin Brockmann, Enza Maria Valente,
Richard J Youle, Anne Gru"newald, Christine Klein. Mitochondrial
damage-associated inflammation highlights biomarkers in PRKN/PINK1
parkinsonism. Brain, 2020; DOI: 10.1093/brain/ awaa246 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201014114603.htm

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