A mechanism that protects brain cells from the effects of aging appears to be weakened in Parkinson’s disease (PD), according to research in the November 22, 2016 edition of Nature Communications. The results suggest that this mechanism may underlie to brain cell loss in Parkinson’s, and points to a new therapeutic approach: boosting the brain’s own protective processes.
Many scientists are studying the role of the mitochondria — powerhouses of the body’s cells — in PD. Scientists have shown that as people age, mutations in mitochondrial DNA build up, leading mitochondria to break down. It turns out that brain cells in the area of the brain affected by PD are particularly susceptible. Yet healthy mice are able to make up for the damage by producing healthy DNA.
Researchers led by Charalampos Tzoulis, M.D., Ph.D., at Norway’s University of Bergen, wondered if this happens in people too. For the new study, they analyzed mitochondrial DNA from healthy individuals aged 11 to 87 years to identify mitochondrial mutations that occur with aging. Then they studied dopamine neurons, the brain cell affected by PD, from 10 people with PD and 10 individuals who died without PD matched for age and sex.
- The type of mutation that occurs in mitochondrial DNA with aging and with PD is a deletion, meaning a section of DNA is missing.
- Dopamine neurons from people with PD had significantly higher levels of deletions in mitochondrial DNA than did neurons from healthy individuals.
- In people without PD, as brain cells aged, the cells made more healthy mitochondrial DNA to compensate for the damaged mitochondrial DNA.
- In people with PD, brain cells did not make new, healthy mitochondrial DNA. The cells had more damaged mitochondrial DNA than healthy.
What Does It Mean?
This study adds to growing evidence pointing to a possible mechanism underlying brain cell loss in PD — the mitochondria’s inability to repair itself.
The results suggest that in healthy people, brain cells stay in balance by producing new mitochondrial DNA. But in PD, this balance is upset and there’s much damaged DNA in the mitochondria. This may lead to brain cell loss in PD.
Based on this, scientists suggest a possible approach for new therapies — increasing levels of healthy mitochondrial DNA in the brain. More research is needed to explore this novel approach to designing new PD therapies.
Dölle C, Flones I, Nido GS, et al. (2017 CK). Defective Mitochondrial DNA Homeostasis in the Substantia Nigra in Parkinson Disease. Nature Communications, DOI: 10.1038/ncomms13548 http://dx.doi.org/10.1038/ncomms13548