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“Powerhouse”-failure may cause Parkinson disease

A new study from the University of Bergen suggests that Parkinson’s disease may be caused by failure of the microscopic powerhouses of the cell, called mitochondria, to adapt to the effects of aging.

Charalampos Tzoulis (to the right) and Christian Dölle (to the left)
Charalampos Tzoulis (to the left) and Christian Dölle (to the right) may have found the reason why someone develops Parkinson disease.
Photo:
UiB

Mitochondria convert foodstuffs (nutrients) into fuel, providing our bodies with the energy they need. It has been known for some time that mitochondria accumulate damage in their DNA with aging and if this reaches high enough levels, it can lead to dysfunction of the energy generators and disease.  

The new study discovered that dopamine-producing neurons of healthy individuals are able to compensate for the buildup of damage in their mitochondria by producing more mitochondrial DNA to replace the one that is faulty.

“Surprisingly, this protective mechanism fails in persons with Parkinson’s disease resulting in gradual loss of the healthy pool of mitochondrial DNA,“ says Dr. Tzoulis, who directs the project at UiB and Haukeland University Hospital.

Possible key to new treatment

The loss of healthy mitochondrial DNA has serious consequences, as it could lead to a number of malfunctions in mitochondria, causing energy deficiency and leakage of dangerous byproducts. Interestingly, mitochondrial DNA damage accumulates at particularly high levels in dopamine-producing brain cells from a region of the brain called “substantia nigra”, which is always and severely affected by Parkinson’s disease.

“I believe we have found an essential biological mechanism which is hardwired into our brain to protect it from mitochondrial aging,” says Dr Tzoulis.

“What intrigues us the most is that this mechanism appears to fail in Parkinson’s disease exposing the brain to the effects of constantly accumulating mitochondrial damage. I believe this to be an important advancement in our understanding of brain aging and Parkinson’s disease and may hold the key for developing new therapies.”

Confirms earlier findings

Parkinson’s disease is one of the most common brain disorders. In spite of intensive research in the field, there is no cure and patients die prematurely due to increasing disability. The research team from Bergen hope that their findings may bring us a step closer to developing a cure for Parkinson’s disease.  

“It has been shown for instance, that drugs increasing the number of mitochondria may be protective for Parkinson’s disease. Our findings may partly explain this observation. That being said, further work will be necessary to understand why mitochondrial compensation fails in Parkinson’s disease and whether it can be exploited for treatment,” concludes Tzoulis.

Dölle C, Flønes I, Nido GS, Miletic H, Osuagwu N, Kristoffersen S, Lilleng PK, Larsen JP, Tysnes OB, Haugarvoll K, Bindoff LA, and Tzoulis C. Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease.

The findings were published on the 22nd of November 2016 in the open-access journal Nature Communications (http://www.nature.com/ncomms/).