A gene could prevent Parkinson's disease

Date:
March 17, 2022
Source:
Universite' de Gene`ve
Summary:
Parkinson's disease is a neurodegenerative disorder characterized
by the destruction of a specific population of neurons: the
dopaminergic neurons. A team has investigated the destruction of
these dopaminergic neurons using the fruit fly as study model. The
scientists identified a key protein in flies, and also in mice,
which plays a protective role against this disease and could be
a new therapeutic target.



FULL STORY ========================================================================== Parkinson's disease is a neurodegenerative disorder characterized by
the destruction of a specific population of neurons: the dopaminergic
neurons. The degeneration of these neurons prevents the transmission
of signals controlling specific muscle movements and leads to tremors, involuntary muscle contractions or balance problems characteristic of this pathology. A team from the University of Geneva (UNIGE) has investigated
the destruction of these dopaminergic neurons using the fruit fly as
study model. The scientists identified a key protein in flies, and also
in mice, which plays a protective role against this disease and could
be a new therapeutic target. This work can be read in the journal Nature Communications.


========================================================================== 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 the Fer2 gene,
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.

In a previous study, this scientific team demonstrated that a mutation in
the Fer2 gene 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 of Fer2 causes Parkinson's
disease-like conditions, the researchers tested whether -- on the
contrary -- an increase in the amount of Fer2 in 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 overproduce Fer2, confirming the hypothesis of its protective role.

"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," explains Federico Miozzo, researcher in the Department of Genetics and Evolution and first author of the study.

A new therapeutic target To find out whether Fer2 plays the same role
in mammals, the biologists created mutants of the Fer2homolog 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 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," concludes Emi Nagoshi.


========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Federico Miozzo, Eva P. Valencia-Alarco'n, Luca Stickley, Michae"la
Majcin Dorcikova, Francesco Petrelli, Damla Tas, Nicolas Loncle,
Irina Nikonenko, Peter Bou Dib, Emi Nagoshi. Maintenance
of mitochondrial integrity in midbrain dopaminergic neurons
governed by a conserved developmental transcription factor. Nature
Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29075-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220317111909.htm

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