Researchers at the University of Geneva (UNIGE) have identified a gene that codes for a protein that has a protective effect against the degeneration of dopaminergic neurons, which could serve as a target in novel treatments for Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disorder that involves the degeneration of populations of dopaminergic neurons in the brain. Dopaminergic neurons have extensive branching and require considerable amounts of energy to send signals throughout their extensive networks. When these neurons run out of energy they degenerate. Considerable research is being conducted into ways to protect these neurons, and thus prevent the development of Parkinson’s disease.
The UNIGE researchers have been investigating the mechanisms involved in the degradation of these neurons using a fruit fly model. Specifically, the researchers have been studying a gene known as Fer2, which has a human counterpart that codes for a protein that controls the expression of several genes. It is possible that a mutation in the gene could play a key role in the development of Parkinson’s disease.
The researchers previously determined that mutations in the Fer2 gene cause Parkinson’s-like deficiencies in fruit flies, such as a delay in the initiation of movement as well as changes to the mitochondria – which are involved in energy production – that are similar to the changes seen in the mitochondria of human patients with Parkinson’s disease.
Since a defective Fer2 gene can cause Parkinson’s-like symptoms, the researchers explored whether an increase in Fer2 could have a protective effect. The researchers determined that Fer2 does have a protective effect and prevents dopaminergic neuron degradation in fruit flies when Fer2 is overexpressed. This was demonstrated by exposing the flies to free radicals, which trigger oxidative stress that causes dopaminergic degradation. When Fer2 is overexpressed, the oxidative stress did not have any effect, suggesting Fer2 is protecting against dopaminergic neuron degradation
The researchers also determined that Fer2-regulated genes are mainly involved with mitochondrial functions and control the function and structure of mitochondria. The researchers explored whether Fer2 has a similar function in humans by creating mutants of the Fer2 homolog in mouse dopaminergic neurons and found that they resulted in similar abnormalities in mitochondria, which caused similar Parkinson’s-like locomotion abnormalities in the mice.
“We are currently testing the protective role of the Fer2 homolog in mice and results similar to those observed in flies would allow us to consider a new therapeutic target for Parkinson’s disease patients,” said study lead, Emi Nagoshi, Professor in the Department of Genetics and Evolution at the UNIGE Faculty of Science.
You can read more about the study in the paper – Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor – which was recently published in Nature Communications. DOI: 10.1038/s41467-022-29075-0