A protein could play a vital protective role against Parkinson’s disease, a Swiss study has found.
The disease is characterised by the destruction of dopaminergic neurons, which prevents the transmission of signals controlling specific muscle movements and leads to tremors, involuntary muscle contractions or balance problems characteristic of this pathology.
However, a team from the University of Geneva (UNIGE), using the fruit fly as a study model, found a protein in flies, and in mice, playing a protective role against the disease. It could be a new therapeutic target.
Their findings are published in Nature Communications.
The laboratory of Professor Emi Nagoshi, from the Faculty of Science’s Department of Genetics and Evolution, uses the fruit fly to study the mechanisms of dopaminergic neuron degeneration.
The group focuses on the Fer2 gene, whose human homolog encodes a protein that controls the expression of other genes and whose mutation could lead to Parkinson’s disease, although the mechanisms for that are not yet well understood.
Its previous study, the researchers found a mutation in the Fer2 gene that causes Parkinson’s-like deficiencies in flies and the team also observed defects in the shape of the mitochondria of dopaminergic neurons, similar to those observed in Parkinson’s patients.
They went on to test if an increase in the amount of Fer2 in the cells could have a protective effect and found when flies are exposed to free radicals, their cells undergo oxidative stress that leads to the degradation of dopaminergic neurons.
However, they observed that oxidative stress no longer has any deleterious effect on the flies if they overproduce Fer2. This, they say, confirms the hypothesis of its protective role.
First author Federico Miozzo, from the Department of Genetics and Evolution, said: “We have also identified the genes regulated by Fer2 and 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.”
When they tested mutants of the Fer2 homolog in mouse dopaminergic neurons, 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 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,” added Prof Emi Nagoshi.
Miozzo F, Valencia-Alarcón EP, Dorcikova MM et al. Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor. Nature Communications 17 March 2022
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