Parkinson’s disease is a brain disorder that affects movement. Parkinson’s disease symptoms usually begin gradually and get worse over time.
The disease affects about 50 percent more men than women. The disease causes include a combination of genetic and environmental factors.
The disorder is mainly characterized by the destruction of the dopaminergic neurons. These small factories within cells are responsible for energy production and activating the cell’s self-destruct mechanisms when damaged. Degeneration of these neurons inhibits the transmission of signals controlling specific muscle movements. It hence leads to shaking, stiffness, tremors, etc.
Scientists at the University of Geneva (UNIGE) have investigated the destruction of these dopaminergic neurons. They used the fruit fly (Drosophila) as a study model. They studied the mechanisms of dopaminergic neuron degeneration.
Scientists, in particular, looked for the Fer2 gene. The human homolog of this gene encodes a protein that controls the expression of many other genes. Plus, the mutation of this gene leads to Parkinson’s disease via mechanisms that are not yet well understood.
A previous study reported that a mutation in the Fer2 gene causes Parkinson’s-like deficiencies in flies. Several defects were also observed in the shape of the mitochondria of dopaminergic neurons. These were similar to those observed in Parkinson’s patients.
Scientists in this study determined whether an increase in Fer2 in the cells could have a protective effect. To test this, they exposed the flies to free radicals. This causes their cells to undergo oxidative stress, prompting degradation of dopaminergic neurons.
Scientists observed that oxidative stress no longer has any deleterious effect on the flies if they overproduce Fer2, confirming the hypothesis of its protective role.
Federico Miozzo, a researcher in the Department of Genetics and Evolution and the study’s first author, said, “We have also identified the genes regulated by Fer2, and these are mainly involved in mitochondrial functions. Therefore, this key protein seems to play a crucial role against the degeneration of dopaminergic neurons in flies by controlling not only the structure of mitochondria but also their functions.”
To see if Fer2 assumes the same role in mammals, scientists created mutants of the Fer2 homolog in mouse dopaminergic neurons. As in the fly, they observed abnormalities in the mitochondria of these neurons and defects in locomotion in aged mice.
Email Nagoshi said, “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.”
- Miozzo, F., Valencia-Alarcón, E.P., Stickley, L. et al. Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor. Nat Commun 13, 1426 (2022). DOI: 10.1038/s41467-022-29075-0