Apart from rare forms involving a single gene, most Parkinson's cases result from an interaction between multiple genetic and environmental risk factors. However, a common element in the onset of the disease is a dysfunction of mitochondria in dopaminergic neurons. These small factories within cells are responsible for energy production, but also for activating the cell's self-destruct mechanisms when damaged.

The laboratory of Emi Nagoshi, Professor in the Department of Genetics and Evolution at the UNIGE Faculty of Science, uses the fruit fly, or Drosophila, to study the mechanisms of dopaminergic neuron degeneration. Her group is particularly interested in theFer2gene, whose human homolog encodes a protein that controls the expression of many other genes and whose mutation might lead to Parkinson's disease via mechanisms that are not yet well understood.

在先前的研究中,这种科学团队demonstrated that a mutation in theFer2gene causes Parkinson's-like deficiencies in flies, including a delay in the initiation of movement. They had also observed defects in the shape of the mitochondria of dopaminergic neurons, similar to those observed in Parkinson's patients.

Protecting neurons

Since the absence ofFer2causes Parkinson's disease-like conditions, the researchers tested whether -- on the contrary -- an increase in the amount ofFer2in the cells could have a protective effect. When flies are exposed to free radicals, their cells undergo oxidative stress which leads to the degradation of dopaminergic neurons. However, the scientists were able to observe that oxidative stress no longer has any deleterious effect on the flies if they overproduceFer2, confirming the hypothesis of its protective role.

"We have also identified the genes regulated byFer2and these are mainly involved in mitochondrial functions. This key protein therefore 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," explains Federico Miozzo, researcher in the Department of Genetics and Evolution and first author of the study.

A new therapeutic target

To find out whetherFer2plays the same role in mammals, the biologists created mutants of theFer2homolog in mouse dopaminergic neurons. As in the fly, they observed abnormalities in the mitochondria of these neurons as well as defects in locomotion in aged mice. "We are currently testing the protective role of theFer2homolog in mice and results similar to those observed in flies would allow us to consider a new therapeutic target for Parkinson's disease patients," concludes Emi Nagoshi.