Degeneration, Neurotransmission, Stress and Aging

Our first research axis focuses on genetic and cellular aspects of degeneration affecting the nervous and cardiac systems. For Parkinson’s disease, we are focusing on several genes already known to be involved in familial and sporadic forms of the disease (specifically SNCA, which codes for α-synuclein, DJ-1and LRRK2), with the aim of better understanding how these genes are involved in disease progression and the degeneration of dopaminergic neurons. In Friedreich’s ataxia, the disease is caused by a decrease in the expression of frataxin, a mitochondrial protein involved in the biosynthesis of iron-sulfur clusters (ISCs). We are studying how frataxin deficiency impacts this essential mitochondrial process, leading to multiple cellular dysfunctions. In the case of cardiomyopathies, our aim is to use Drosophila as a tool for validating new genes and mechanisms, through functional screening of candidate genes identified in patients.

This axis is dedicated to the identification and in vivo evaluation of therapeutic approaches in Drosophila models of Parkinson’s disease and Friedreich’s ataxia.  We are essentially developing two types of approaches:

1) the pharmacological screening of candidate molecules, which are either selected for their known effects on processes affected in the diseases (such as oxidative stress, mitochondrial dysfunction or perturbation of iron homeostasis…) or molecules derived from high-throughput screening in vitro or in silico carried out by our collaborators

2) the research and evaluation of therapeutic peptides. In particular, we are looking for interfering peptides that can destabilize protein-protein interactions involved in physiopathological processes. This area benefits from the expertise of the TMP2I team of the unit.

Environmental conditions can have a deep impact on longevity and age-related neurodegenerative diseases. We are looking at this from two perspectives:

1) the long-term impact, maintained over several generations i.e transgenerational, that variations in environmental factors can have on physiological aging.

2) the effects of environmental exposure to neurotoxic compounds. An increased risk of developing Parkinson’s disease has been observed in people, like farmers, who are exposed for a long period of time to pesticides. Drosophila is a model organism particularly relevant to study the molecular link between pesticide exposure and Parkinson’s disease.