Nuber, Silke and Petrasch-Parwez, Elisabeth and Winner, Beate and Winkler, Juergen and von Hoersten, Stephan and Schmidt, Thorsten and Boy, Jana and Kuhn, Melanie and Nguyen, Huu P. and Teismann, Peter and Schulz, Jorg B. and Neumann, Manuela and Pichler, Bernd J. and Reischl, Gerald and Holzmann, Carsten and Schmitt, Ina and Bornemann, Antje and Kuhn, Wilfried and Zimmermann, Frank and Servadio, Antonio and Riess, Olaf (2008) Neurodegeneration and motor dysfunction in a conditional model of Parkinson's disease. JOURNAL OF NEUROSCIENCE, 28 (10). pp. 2471-2484. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
alpha-Synuclein (alpha-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease. These disorders are characterized by various neurological and psychiatric symptoms based on progressive neuropathological alterations. Whether the neurodegenerative process might be halted or even reversed is presently unknown. Therefore, conditional mouse models are powerful tools to analyze the relationship between transgene expression and progression of the disease. To explore whether alpha-syn solely originates and further incites these alterations, we generated conditional mouse models by using the tet-regulatable system. Mice expressing high levels of human wild-type alpha-syn in midbrain and forebrain regions developed nigral and hippocampal neuropathology, including reduced neurogenesis and neurodegeneration in absence of fibrillary inclusions, leading to cognitive impairment and progressive motor decline. Turning off transgene expression in symptomatic mice halted progression but did not reverse the symptoms. Thus, our data suggest that approaches targeting alpha-syn-induced pathological pathways might be of benefit rather in early disease stages. Furthermore, alpha-syn-associated cytotoxicity is independent of filamentous inclusion body formation in our conditional mouse model.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN ALPHA-SYNUCLEIN; PRESYNAPTIC DOPAMINERGIC NEURON; POSITRON-EMISSION-TOMOGRAPHY; TRANSGENIC MOUSE MODEL; LEWY BODY DEMENTIA; SUBSTANTIA-NIGRA; OLFACTORY-BULB; WILD-TYPE; SUBCELLULAR-LOCALIZATION; MAMMALIAN-CELLS; conditional; alpha-synuclein; neurodegeneration; Parkinson's disease; mouse model; dark cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Nov 2020 11:32 |
| Last Modified: | 05 Nov 2020 11:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31188 |
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