Head of Unit: Thierry Baron
Deputy Head of Unit: Anne-Gaëlle Morignat
The Neurodegenerative Diseases Unit is a team of 11 employees, including five scientists/engineers, five laboratory technicians and a secretary. For several years, it has been studying animal diseases associated with protein folding defects, historically represented by prion diseases. The unit has an approximately 500 m2 platform of conventional and containment level L3 laboratories.
The unit is the National Reference Laboratory for the diagnosis and surveillance of prion diseases in ruminants.
Historically, the unit's work has been dedicated to the study of prion “strains” and their biological and molecular differentiation. It has largely focused on these diseases in laboratory rodents (mice, hamsters). A majority of the work undertaken has dealt with methods for the molecular phenotyping of pathological prion proteins. This work is still ongoing, with an emphasis on prion disease in elks, which recently appeared in Northern Europe. The objective is to determine the origin of the prion responsible for this disease, in particular through comparisons with other prion diseases in ruminants, especially in sheep.
More recently, these methodologies based on the biochemistry of proteins and histopathology (study of tissue) combined with in vitro methods have been implemented to study human neurodegenerative diseases, in particular Parkinson's disease. This work is largely carried out using animal models of Parkinson's or Alzheimer's disease.
Part of this work involves the molecular characterisation of alpha-synuclein aggregation; alpha-synuclein is a protein found in lesions in Parkinson's disease and similar diseases. The work aims to determine how neuropathological lesions spread in the central and peripheral nervous systems as these diseases progress and to what extent protein aggregation characteristics can be useful for the early diagnosis of these diseases or explain why there are diseases that differ in terms of the nature of the lesions and their clinical expression.
A second part focuses on the role of pesticide exposure in Parkinson's disease. The goal of this work is to better understand how much this exposure is a risk factor for this disease. Initially, experimental work was undertaken with paraquat, an herbicide. Now, emphasis is being placed in particular on chlordecone, a persistent insecticide that has been massively used in the Caribbean and is a major human health hazard. Among other things, the team is seeking to understand to what extent a pesticide could initiate and/or promote the spread of protein aggregation. In additional to animal models, in vitro approaches are being developed.
Main research projects, from the last five years and ongoing
Can chlordecone have an adverse effect on the mouse nigrostriatal system, the preferential target in Parkinson's disease?
Chlordecone is an environmental contaminant in the French Caribbean whose acute neurotoxicity is well documented. However, no experimental studies are available concerning the possible chronic neurotoxicity of this insecticide in connection with the potential occurrence of neurodegenerative diseases such as Parkinson's disease. The project is seeking to determine whether repeated exposure to chlordecone in mice could damage the regions of the brain affected in this disease. During this work, the team will also assess to what extent this substance can accumulate in the brain.
Evaluation of peripheral nervous system involvement during the development of a central alpha-synucleinopathy: comparative study of dietary exposure to pesticides in various murine models of Parkinson's disease (2014-2017)
Funding: Thesis project defended by the Auvergne-Rhône-Alpes Region
Molecular study of the spread of α-synuclein aggregation in a transgenic model of Parkinson's disease: impact of b-synuclein overexpression using adeno-associated virus (AAV) vectors (2014-2017)
Funding: Thesis project defended by the Auvergne- Rhône-Alpes Region