Researchers find a cause of Parkinson’s disease
Summary
Mitochondrial DNA damage triggers spread of Parkinson’s disease-like pathology In the field of neurodegenerative diseases, especially sporadic Parkinson’s disease (sPD) with dementia (sPDD), the question of how the disease begins and spreads in the brain remains central. While prion-like proteins have been blamed , recent studies suggest the involvement of additional factors. We found that oxidative stress, impaired DNA binding, cytosolic DNA sensing, and toll-like receptor (TLR) activation pathways are strongly associated with the sPDD transcriptome, which has dysregulated type I interferon (IFN) signaling. In patients with sporadic Parkinson’s disease (sPD), we confirmed mitochondrial (mt)DNA deletions in the medial frontal gyrus, suggesting a potential role of damaged mtDNA in the pathophysiology of the disease. These findings could shed light on new molecular pathways through which damaged mtDNA initiates and spreads PD-like diseases, potentially opening new avenues for therapeutic interventions or disease monitoring. |
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Until recently, our understanding of Parkinson’s disease has been quite limited, which has been evident in the limited treatment and management options for this debilitating condition.
Our recent knowledge has revolved mainly around the genetic factors responsible for familial cases, while the causal factors in the vast majority of patients remained unknown.
However, in a new study, researchers from the University of Copenhagen have revealed new insights into brain functioning in Parkinson’s patients. Leading this groundbreaking discovery is Professor Shohreh Issazadeh-Navikas.
“For the first time, we can show that mitochondria , the vital energy producers within brain cells, particularly neurons, suffer damage, leading to alterations in mitochondrial DNA [LP1]. This starts and spreads the disease like wildfire through the brain,” says Shohreh Issazadeh-Navikas, adding:
"Our findings establish that the spread of damaged genetic material, mitochondrial DNA, causes symptoms reminiscent of Parkinson’s disease and its progression to dementia."
Parkinson’s disease is a chronic condition that affects the central nervous system and causes symptoms such as difficulty walking, tremors, cognitive challenges, and eventually dementia. The disease affects more than 10 million people worldwide. While there is currently no cure, certain medical treatments may offer relief from your symptoms.
Small fragments of mitochondrial DNA spread the disease
By examining the brains of humans and mice, researchers found that damage to mitochondria in brain cells occurs and spreads when these cells have defects in antiviral response genes. They tried to understand why this damage occurred and how it contributed to the disease.
His search led to a remarkable revelation
“Small fragments (actually DNA) from the mitochondria are released into the cell. When these damaged DNA fragments are lost, they become toxic to the cell, causing the nerve cells to expel this toxic mitochondrial DNA,” explains Shohreh Issazadeh-Navikas.
“Given the interconnected nature of brain cells, these toxic DNA fragments spread to neighboring and distant cells, similar to an uncontrolled forest fire caused by a casual bonfire,” he adds.
The dream is a sample of blood
Shohreh Issazadeh-Navikas anticipates that this study marks the initial step toward a better understanding of the disease and the development of future treatments, diagnostics, and measurements of treatment effectiveness for Parkinson’s disease.
He also expressed hope that "the detection of damaged mitochondrial DNA may serve as an early biomarker for disease development."
Biomarkers are objective indicators of specific medical conditions observed in patients. While some biomarkers are common, such as blood pressure, body temperature and body mass index, others provide information about particular diseases, such as genetic mutations in cancer or blood sugar level in diabetes. The identification of a biomarker for Parkinson’s disease holds great promise for improving future treatments.
“It is possible that mitochondrial DNA damage in brain cells leaks from the brain into the blood. "This would allow us to take a small sample of blood from a patient as a way to diagnose early or establish a favorable response to future treatments."
Professor Issazadeh-Navikas also envisages the possibility of detecting damaged mitochondrial DNA in the bloodstream, which would make it feasible to diagnose the disease or assess responses to treatment using a simple blood test.
The researchers’ next effort involves investigating how mitochondrial DNA damage can serve as predictive markers for different stages and progression of the disease. "In addition, we are dedicated to exploring potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in the disease."
