caa a22 4500 463254511 CHVBK 20180405153350.0 cr unu---uuuuu 170326e20070601xx s 000 0 eng 10.1007/s10571-007-9141-5 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9141-5 Predominant Neuritic Pathology Induced by Viral Overexpression of α -Synuclein in Cell Culture [Elektronische Daten] [S. Zach, H. Bueler, B. Hengerer, F. Gillardon] 1. Alpha-synuclein is known to play an important role in the pathogenesis of Parkinson's disease (PD). The pathogenicity of α-synuclein is related to its ability to form intraneuronal inclusions. The inclusions, which are found in brains of patients with PD and diffuse Lewy body disease consist partially of C-terminally truncated α-synuclein. This α-synuclein species has an increased ability to form aggregates compared to full length α-synuclein. 2. We have used an adeno-associated virus (AAV) vector system to overexpress either C-terminally truncated or full length α-synuclein containing the A53T mutation, which have both been identified in brains of familial PD patients and transgenic mouse models. Dissociated mesencephalic neurons, cerebellar granule neurons, and organotypic midbrain slice cultures were infected with AAV containing the transgene under the control of the cytomegalovirus promoter. 3. We demonstrate that viral overexpression of α-synuclein(A53T) leads to the formation of distorted neurites, intraneuritic swellings, and granular perikaryal deposits in cultured neurons. Our results indicate that these cell culture models may represent an early phase of PD reflecting pathologic neuritic alterations before significant neuronal cell loss occurs. Springer Science+Business Media, LLC, 2007 Parkinson's disease nationallicence mesencephalic neurons nationallicence neurodegeneration nationallicence adeno-associated virus nationallicence neuritic swellings nationallicence truncated α-synuclein nationallicence AAV : adeno-associated virus nationallicence AD : Alzheimer's disease nationallicence CGN : cerebellar granule neuron nationallicence CMV : cytomegalovirus nationallicence CSPα : cystein-string-protein-α nationallicence DA : dopaminergic nationallicence EGFP : enhanced green fluorescent protein nationallicence HBSS : Hank's balanced salt solution nationallicence PD : Parkinson's disease nationallicence TUNEL : terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling nationallicence WT : wild-type nationallicence Zach S. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut Bueler H. Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland aut Hengerer B. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut Gillardon F. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 505-515 0272-4340 27:4<505 2007 27 10571 https://doi.org/10.1007/s10571-007-9141-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9141-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zach S. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut NATIONALLICENCE 700 1- Bueler H. Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland aut NATIONALLICENCE 700 1- Hengerer B. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut NATIONALLICENCE 700 1- Gillardon F. Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 505-515 0272-4340 27:4<505 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer