The François Jacob Institute of Biology brings together five departments and three services
The last two years in scientific news
Highlight | News | Scientific result | Neurodegenerative diseases | Parkinson's disease
As part of an international partnership, a team from the Neurodegenerative Diseases Laboratory (MIRCen) has characterized the pathological effects of various alpha-synuclein aggregate strains in vivo. In their work, published in
Acta Neuropathologica Communications, the researchers showed that the conformation of these aggregates plays a key role in their amplification and propagation in the brain.
term synucleinopathies covers a group of neurodegenerative diseases (including
Parkinson's disease, Lewy body dementia and multiple system atrophy)
characterized by the accumulation of abnormal aggregates of the protein
alpha-synuclein in the brain.
normal, soluble and monomeric form, alpha-synuclein plays an important role in
the normal development of cognitive functions. In synucleinopathies however, it
forms toxic, insoluble, fibrillar aggregates that comprise the primary
structural component of "Lewy bodies", a characteristic feature of these
diseases. These aggregates propagate from one neuron to another, leaving in
their wake progressive and irreversible neural degeneration, the manifestations
of which vary according to the synucleinopathy in question.
fibrillar agglomerations are polymorphic, that is, they take on different
forms, called conformational strains, each presenting its own biochemical,
structural and physical characteristics. The clinical heterogeneity observed in
synucleinopathies suggests that there may be a link between the strains and the
different pathological manifestations of the diseases.
explore that possibility, researchers from the Neurodegenerative Diseases
Laboratory (MIRCen) partnered with a team from the American Van Andel Institute
to characterize the propagation profiles of five distinct alpha-synuclein
conformational strains from the olfactory bulb, a brain region affected
early in both Parkinson's disease and Lewy body dementia.
showed that the five strains propagated from the bulb to distinct regions of
the brain known to be affected later in the course of disease. Their analysis
of the affected cerebral regions, the speed of propagation to them and the
resulting diseases indicated specific pathological processes for each of the
specific conformations of the alpha-synuclein assemblies were also shown to be
determinant for the speed of aggregate amplification and propagation within the
international study opens new doors toward the development of specific
therapeutic strategies for the range of synucleinopathies via a more precise
characterization of alpha-synuclein aggregates in patients.
α-Synuclein conformational strains spread, seed and
target neuronal cells differentially after injection into the olfactory bulb I Acta
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.