Fragments of mitochondrial DNA spread Parkinson's disease

Parkinson’s disease is a chronic condition that affects the central nervous system, leading to symptoms such as difficulty walking, tremors, cognitive challenges and, eventually, dementia. Until recently, our understanding of this debilitating condition has been quite limited; now, researchers from the University of Copenhagen have unveiled new insights into the workings of the brain in Parkinson’s patients, with their results published in the journal Molecular Psychiatry.

“For the first time, we can show that mitochondria — the vital energy producers within brain cells, particularly neurons — undergo damage, leading to disruptions in mitochondrial DNA,” said study leader Professor Shohreh Issazadeh-Navikas. “This initiates and spreads the disease like a wildfire through the brain.

“Our findings establish that the spread of the damaged genetic material, the mitochondrial DNA, causes the symptoms reminiscent of Parkinson’s disease and its progression to dementia.”

By examining both human and mouse brains, researchers discovered that the damage to mitochondria in brain cells occurs and spreads when these cells have defects in anti-viral response genes. They sought to understand why this damage occurred and how it contributed to the disease. Their search led to a remarkable revelation.

“Small fragments of … DNA from the mitochondria are released into the cell,” Issazadeh-Navikas said. “When these fragments of damaged DNA are misplaced, they become toxic to the cell, prompting nerve cells to expel this toxic mitochondrial DNA.

“Given the interconnected nature of brain cells, these toxic DNA fragments spread to neighbouring and distant cells, similar to an uncontrolled forest fire sparked by a casual bonfire.”

Issazadeh-Navikas envisions that this study marks an initial stride towards a better understanding of the disease, and the development of future treatments, diagnostics and measurement of treatment efficacy for Parkinson’s disease. She also expressed hope that “detecting the damaged mitochondrial DNA could serve as an early biomarker for disease development”.

“It could be possible that the damage of the mitochondrial DNA in the brain cells leaks from the brain into the blood; that would make it possible to take a small sample of a patient’s blood as a way of diagnosing early on or to establish the favourable response to future treatments,” Issazadeh-Navikas said. She also envisions the possibility of detection of damaged mitochondrial DNA in the bloodstream, making it feasible to diagnose the disease or gauge treatment responses through a simple blood test.

The researchers’ next endeavour involves investigating how mitochondrial DNA damage can serve as predictive markers for different disease stages and progression. “Furthermore,” Issazadeh-Navikas said, “we are dedicated to exploring potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in the disease.”

Image credit: iStock.com/Alexey Koza