Prion-like Dissemination of Synuclein Pathology: A Non-human Study
Research Grant, 2013
Parkinson’s disease (PD) is characterized by the loss of midbrain dopaminergic neurons and the presence of aggregates named Lewy bodies. This pathology is believed to drive the progression of the disease process. Recent data suggest that alpha-synuclein, a major protein component of Lewy bodies, may be responsible for the spreading of the pathological process within affected individuals. However, the potential of Lewy bodies to initiate and propagate PD-related pathology is unknown.
Based upon preliminary data collected in pre-clinical models, we will first extract Lewy bodies from post-mortem PD brains. Once those have been characterized, the pure Lewy body samples will be injected into the brain and the gut of models, which will then be followed for two years. Behavior will be assessed and subgroups terminated at regular intervals to monitor progression of dopamine neuron degeneration.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This research will provide information on the process and time course of neurodegeneration and the interaction between Lewy bodies and healthy alpha-synuclein.
The study will demonstrate that alpha-synuclein species contained in Lewy bodies may spread the pathological process in PD, whatever the place of “contamination” (i.e. within the dopamine-sensitive areas or the cortex or even the gut). If proven, the effort will also provide a unique experimental set-up for testing disease-modifying strategies.
INSERM Research Director at Institute of Neurodegenerative Diseases, CNRS UMR 5293, University Victor Segalen
Location: Bordeaux, France