Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Découvertes et avancées | Scientific result | Parkinson's disease | Structural biology | Proteomics
As part of a European collaboration, researchers at the CEA-Jacob have demonstrated that exposure to aggregates of α-synuclein proteins could reduce the support capacity of the brain's immune cells, the astrocytes.
Parkinson's disease results from the loss of dopaminergic neurons, which produce dopamine and are notably involved in the regulation of movement. The disease is characterized by the presence of Lewy bodies, which are toxic clusters composed mostly of an abnormal, aggregated form of the protein α-synuclein. These aggregates are transferred from affected neurons to healthy neurons as well as astrocytes, immune cells in the brain with a role in neuronal support. However, little is known about the connection between their accumulation, their effect on astrocytes, and their impact on neuronal lesions resulting from the disease.
In collaboration with Lund University, MIRCen researchers at the Institut Jacob have brought to light a new role for astrocytes in Parkinson's disease.
To achieve this, they differentiated stem cells taken from healthy individuals and patients with Parkinson's disease into astrocytes. They next exposed these astrocytes to different types of α-synuclein aggregates and observed that the cells develop a process in which the aggregates are digested into smaller fragments and transported to the cell surface to be recognized by the immune system.
The researchers also showed that exposure of astrocytes derived from Parkinson's patients to α-synuclein aggregates leads to a decrease in their respiratory metabolism and a reduction in the secretion of certain inflammatory proteins. These results suggest that the degeneration of dopaminergic neurons in Parkinson's disease is due to decreased support from astrocytes.
This research also shows that while astrocytes are able to degrade small aggregates, this is not the case for very large aggregates, similar to those observed in the advanced stages of the disease. These results underline the importance of identifying an early therapeutic window for future treatments of Parkinson's disease. Indeed, if the processes are too advanced and the aggregates too large, it will not be possible to degrade these structures and halt or reverse disease progression.
This work should lead to the design of new therapeutic approaches aimed at delaying disease progression through the astrocytes.
TNF-α and α-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration I Cell Reports.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.