Session Information
Date: Tuesday, June 6, 2017
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To define the kinetics of neuronal and astrocytic abnormalities induced by human-derived α-syn aggregates for grounding the use of such system to identify and test putative therapeutic compounds.
Background: Synucleinopathies are a group of diseases characterized by the presence of intracellular protein aggregates containing α-synuclein (α-syn). While α-syn aggregates have been shown to induce multimodal cellular dysfunctions, uptake and transport mechanisms remain unclear.
Methods: Using high-throughput imaging on cortical neurons and astrocytes, we here define the kinetics of neuronal and astrocytic abnormalities induced by human-derived α-syn aggregates grounding the use of such system to identify and test putative therapeutic compounds. We then aimed at characterizing uptake and transport mechanisms using primary cultures of cortical neurons and astrocytes either in single well or in microfluidic chambers allowing connection between cells and cell-types.
Results: We report that astrocytes take up α-syn-aggregates far more efficiently that neurons through an endocytic event. We also highlight that active α-syn transport occurs between cells and any cell-types. Of special interest regarding the disease, we also show that uptake and spreading of α-syn from astrocytes to neurons can lead to neuronal death. We show using high-throughput screening a concentration-dependent toxicity of patients- derived α-synuclein aggregates. Then using microfluidic chambers, we report that α-syn aggregates are taken up by both neurons and astrocytes and can spread between cell-types leading to neuronal death.
Conclusions: Altogether these results lead us to propose a simple mechanism of production of a-syn toxic species and stabilization towards thermodynamically harmful species by the sole virtue of the host response to exogenous a-syn.
To cite this abstract in AMA style:
E. Bezard, F. Cavaliere, L. Cerf, B. Dehay, P. Ramos-Gonzalez, F. De Giorgi, M. Bourdenx, A. Bessede, J. Obeso, F. Ichas, C. Matute. a-synuclein neurotoxicity and spreading using Lewy Body extracts from Parkinson Disease Brains: In vitro screening by cell-based assays [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/a-synuclein-neurotoxicity-and-spreading-using-lewy-body-extracts-from-parkinson-disease-brains-in-vitro-screening-by-cell-based-assays/. Accessed June 15, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-synuclein-neurotoxicity-and-spreading-using-lewy-body-extracts-from-parkinson-disease-brains-in-vitro-screening-by-cell-based-assays/