PARKINSON DISEASE – α-syn

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Parkinson’s disease (PD) is a neurodegenerative disease that causes involuntary or uncontrollable movements. The most prominent signs and symptoms of PD occur when dopaminergic neurons in the basal ganglia degenerate. Their degeneration leads to decreased dopamine production and abnormal aggregation of alpha-synuclein (α-Syn), a key peptide located primarily in presynaptic terminals, and strongly linked genetically and pathologically to PD. Currently, scientists still do not know what causes the degeneration of dopaminergic neurons and the aggregation of α-Syn.

We have developed at NETRI microfluidic devices with an asymmetric architecture coupled with high-throughput compatible MultiElectrod Arrays (MEAs), in collaboration with Axion BioSystems. These devices allow the creation of synapses and neurons functional activity recording to study the α-Syn aggregation and its impact on the dopaminergic neurons network.

-                                        CAPABILITIES
+                                        Synaptic isolation, Functional Activity, 

Co-culture,

 hiPSC Derived Cell, 

 Readouts
-                                        CHIP
+                                        DuaLink Shift MEA
-                                        CELL TYPE
+                                        Dopaminergic Neurons & GABAergic Neurons
-                                        RESOURCES
+                                        Publications,



Application Note,


Application Protocol,


Posters,


Cells DataSheet
+                                        (FujiFilm CDI, BrainXell),
Chip DataSheet
-                                        RELEATED PAPERS
+                                        Tran, H. T., Chung, C. H. Y., Iba, M., Zhang, B., Trojanowski, J. Q., Luk, K. C., & Lee, V. M. Y. (2014). α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration. Cell Reports, 7(6), 2054–2065.
+                                        Tran, H. T., Chung, C. H. Y., Iba, M., Zhang, B., Trojanowski, J. Q., Luk, K. C., & Lee, V. M. Y. (2014). α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration. Cell Reports, 7(6), 2054–2065. 


Gribaudo, S., Tixador, P., Bousset, L., Fenyi, A., Lino, P., Melki, R., Peyrin, J. M., & Perrier, A. L. (2019). Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network. Stem Cell Reports, 12(2), 230–244.



Fernandes, J. T. S., Chutna, O., Chu, V., Conde, J. P., & Outeiro, T. F. (2016). A novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson’s disease and other synucleinopathies. Frontiers in Neuroscience, 10(NOV), 1–11. 


Freundt, E. C., Maynard, N., Clancy, E. K., Roy, S., Bousset, L., Sourigues, Y., Covert, M., Melki, R., Kirkegaard, K., & Brahic, M. (2012). Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport. Annals of Neurology, 72(4), 517–524. 


Lu, X., Kim-han, J. S., Malley, K. L. O., & Sakiyama-elbert, S. E. (2012). Short communication A microdevice platform for visualizing mitochondrial transport in aligned dopaminergic axons. 209, 35–39. 



Prots, I., Grosch, J., Brazdis, R. M., Simmnacher, K., Veber, V., Havlicek, S., Hannappel, C., Krach, F., Krumbiegel, M., Schütz, O., Reis, A., Wrasidlo, W., Galasko, D. R., Groemer, T. W., Masliah, E., Schlötzer-Schrehardt, U., Xiang, W., Winkler, J., & Winner, B. (2018). α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies. Proceedings of the National Academy of Sciences of the United States of America, 115(30), 7813–7818. 


Brahic, M., Bousset, L., Bieri, G., Melki, R., & Gitler, A. D. (2016). Axonal transport and secretion of fibrillar forms of α-synuclein, Aβ42 peptide and HTTExon 1. Acta Neuropathologica, 131(4), 539–548. 


Cavaliere, F., Cerf, L., Dehay, B., Ramos-gonzalez, P., De Giorgi, F., Bourdenx, M., Bessede, A., Obeso, J. A., Matute, C., Ichas, F., Bezard, E., Giorgi, F. De, Bourdenx, M., Bessede, A., Obeso, J. A., Matute, C., Ichas, F., & Bezard, E. (2017). In vitro α-synuclein neurotoxicity and spreading among neurons and astrocytes using Lewy body extracts from Parkinson disease brains. Neurobiology of Disease, 103, 101–112.


Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M. Y. (2011). Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death. Neuron, 72(1), 57–71.
-                                        READINESS LEVEL
+                                        ④/ ⑧ Protocol done for each cell types

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PARKINSON DISEASE – α-syn

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