Mitochondrial dysfunction is shown to be the leading cause of Parkinson’s


A detailed view of what happens to neurons. Credit: University of Copenhagen

12,000 people in Denmark and 7 to 10 million people worldwide suffer from Parkinson’s disease (PD). It is the second most common neurogenerative disorder in aging and the most common movement disorder, but the cause of the disease is largely unknown.

In a new study, researchers at the University of Copenhagen show that the most common form of the disease, which covers between 90 and 95 percent of all cases of Parkinson’s disease known as sporadic PD, is caused by a blockage. of a pathway that regulates the central nerve cell. , the mitochondria.

“Just like when people eat, the cells take what they need and get rid of the rest of the waste products. But if it’s ours having this specific type of signaling blockage means that the central cell (mitochondria) cannot be cleaned after being damaged, ”explains Professor Shohreh Issazadeh-Navikas, author and leader of the corresponding group, at Biotech Research & Innovation Center.

Blockage causes an accumulation of high amounts of damaged mitochondria, although it is not able to produce enough energy for cells. It causes neurons to die gradually, which is the reason for the development of Parkinson’s disease symptoms, and why it leads to dementia.

Blockade is caused by a deregulation of immune genes, more specifically by a pathway called interferon type 1, which is usually important in fighting viruses, but we are now showing that it is also responsible for regulating the energy supply of nerve cells.

“We need to regulate all parts of our body. We have a signal to stop eating when we are full and the same thing happens to any other part of our body. If we have an infection, some parts of our body have to fight it and prevent it. but when the infection clears up, the signal should decrease.This is the work of a protein called PIAS2.This causes blockage of the type 1 interferon pathway and, when the infection is over, blockage “Stop it and get back to normal. But that doesn’t seem to be the case in patients with Parkinson’s disease. In addition, we show that this deregulation causes a defect in the mitochondrial energy supply, as mentioned above,” he says. Issazadeh-Navikas.

These pathways are very important for brain function, but are also associated with microbial and virus recognition. For example, they are very important in combating COVID-19 and a mutation in the related gene has been shown to be related to a fatal outcome after contracting COVID-19.

The researchers combined and analyzed four , who studied neurons in the brain with Parkinson’s disease and examined what types of genes they express.

They then examined which genetic patterns were altered in patients with Parkinson’s disease, and especially those who had also developed PD with dementia.

In order to test the results, the main results of the combined data were tested in three different mouse models using a negative type I interferon pathway regulator, PIAS2, which had been identified from the study. of patients as one of the key proteins related to the progression of Parkinson’s disease and dementia.

“We show that a high accumulation of PIAS2 protein is what is causing pathway blockade, which should have activated the processes responsible for removing damaged proteins and mitochondrial debris,” says Issazadeh-Navikas.

“Accumulation of damaged mitochondrial mass leads to an increase in other toxic proteins. Therefore, when we compare patients with healthy patients of the same age without Parkinson’s disease, we see that this PIAS2 protein is highly expressed in neurons, which is why this pathway should be evaluated for possible roles in the other forms of familial Parkinson’s disease that we have not studied here. “

Researchers hope the study will encourage research to counter the pathway , which could have a beneficial impact on the and towards the prevention of dementia.

In the next stages, the Issazadeh-Navikas group will study how contributes to neuronal homeostasis and survival, as well as how their deregulation causes neuronal cell death.

The immune gene prevents Parkinson’s disease and dementia

More information:
Joana Magalhaes et al, PIAS2-mediated blockade of IFN-β signaling: a basis for sporadic dementia from Parkinson’s disease, Molecular psychiatry (2021). DOI: 10.1038 / s41380-021-01207-w

Citation: Mitochondrial malfunction is shown to be the leading cause of Parkinson’s (2021, July 9) recovered on July 9, 2021 at major-parkinson.html

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