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Updated: Jul 20, 2026

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
Mechanisms and models of alpha-synuclein-related neurodegeneration
Wolfdieter Springer1, Philipp J Kahle
1Laboratory of Functional Neurogenetics,Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University Clinics Tübingen, Otfried-Müller-Strasse 27, 72076 Tübingen, Germany. Philipp.Kahle@Uni-Tuebingen.de
Abstract:
Expression of the Parkinson's disease-associated protein alpha-synuclein causes formation of aggregates and cytotoxicity in a great diversity of transgenic model organisms, in the case of Drosophila melanogaster affecting specific dopaminergic neuron clusters. The relative contribution of alpha-synuclein misfolding and phosphorylation for neurodegeneration was elucidated in these systems. In transgenic mice, typical neuropathologic inclusions formed concomitant with behavioral deficits, reminiscent of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Neuronal degeneration was cell-autonomous in the Lewy body disease models, whereas gliotic changes accompanied neurodegeneration caused by (oligodendro)glial cytoplasmic inclusions. These recent findings provided major insights into the molecular mechanisms of alpha-synucleinopathies.
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