Universitätsklinik für Neurologie

Arbeitsgruppe Neurodegenerative Erkrankungen

Movement Disorders Unit Innsbruck




Leistungsbericht / Publications



Univ.-Prof. Dr. Werner Poewe 
Priv. Doz. Dr. Sylvia Bösch
Univ-Prof. Dr. Christoph Scherfler
Univ-Prof. Dr. Klaus Seppi
Univ.-Prof. Dr. Gregor K. Wenning

Dr. Susanne Dürr
Dr. Alessandra Fanciulli
Ass.-Prof. Dr. Roberta Granata
Dr. Eva Hametner
Dr. Anna Hotter
Dr. Anna Hussl
Dr. Florian Krismer
Dr. Philipp Mahlknecht
Dr. Katherina Mair  
Dr. Wolfgang Nachbauer
Dr. Michael Nocker
Dr. Sabine Spielberger
Dr. Fabienne Sprenger
Priv. Doz. Dr. Nadia Stefanova
Dr. Heike Stockner




Experimentelle Neurodegenerationsforschung

(Stefanova / Reindl / Wenning, 2001, 2002, 2003)
Stefanova N, Klimaschewski L, Poewe W, Wenning GK, Reindl M (2001). Glial Cell Death Induced by Overexpression of alpha-Synuclein. J Neurosci Res 65: 432-438. AG_ND_1
alpha-synuclein positive GCIs in MSA
Stefanova N, Emgård M, Klimaschewski L, Wenning GK, Reindl M (2002). Ultrastructure of alpha-Synuclein Positive Aggregations in U373 Astrocytoma and Rat Primary Glial Cells. Neurosci Lett 232: 37-40.  AG_ND_2
apoptosis in MSA oligodendrocytes
Stefanova N, Schanda K, Klimaschewski L, Poewe W, Wenning GK, Reindl M (2003). Tumor necrosis factor alpha induced cell death in U373 cells overexpressing alpha-synuclein. J Neurosci Res 73: 334-340.  AG_ND_5
alpha-synuclein positive cytoplasmic inclusions in glial cell culture with ultrastructure that resembles that of GCIs in MSA


Alpha-Synuclein is present in intracellular protein aggregates that are hallmarks of common neurodegenerative disorders including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. alpha-Synuclein is localized in neurons and presynaptic terminals. Under pathological conditions, however, it is also found in glia. The role of alpha-synuclein in glial cells and its relevance to the molecular pathology of neurodegenerative diseases is presently unclear. To investigate the consequence of alpha-synuclein overexpression in glia, we transfected U373 astrocytoma cells with vectors encoding wild-type human alpha-synuclein or C-terminally truncated synuclein fused to red fluorescent protein. alpha-synuclein immunocytochemistry of transfected astroglial cells revealed diffuse cytoplasmic labeling associated with discrete inclusions both within cell bodies and processes. Susceptibility to oxidative stress was increased in astroglial cells overexpressing alpha-synuclein, particularly in the presence of cytoplasmic inclusions. Furthermore, overexpression of alpha-synuclein induced apoptotic death of astroglial cells as shown by TUNEL staining. We have additionally overexpressed wild-type and a C-terminally truncated form of alpha-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form alpha-synuclein-positive aggregations in vitro perinuclearly or in the processes of the cells.
Morphological studies demonstrate that the aggregations we have observed in vitro are not limited by a membrane but have unclear borders. They have an amorphous dense core that is intensely alpha-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are alpha-synuclein-immunoreactive. We conclude that this in vitro model of alpha-synuclein-positive glial aggregations mimics the morphology of the abnormal glial inclusions described in neurodegenerative disorders and could be a suitable model for studying their role in the pathogenesis of these diseases.
Microglial activation in Parkinson disease and multiple system atrophy suggests that neuroinflammatory responses might interact with alpha-synuclein and contribute to the pathogenesis of these disorders. To study the role of tumor necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine produced by microglia, on cells overexpressing alpha-synuclein we have used the astrocytoma cell line U373 engineered to express C-terminally truncated alpha-synuclein as a fusion protein with red or green fluorescent proteins. We demonstrate that alpha-synuclein overexpression augmented TNF-alpha-induced apoptotic cell death in U373 cells by induction of caspase activation. Furthermore, TNF-alpha exposure was associated with significant cytoskeletal changes characterized by altered inclusion composition with loss of cytoskeletal proteins and elevation of high-molecular-weight alpha-synuclein species. We conclude that alpha-synuclein overexpression significantly increases the vulnerability of U373 cells to apoptosis through TNF-alpha-mediated pathways.

Neuroimaging bei Parkinson Symptomen


Schocke MF, Seppi K, Esterhammer R, Kremser C, Jaschke W, Poewe W, Wenning
GK.Diffusion-weighted MRI differentiates the Parkinson variant of multiple system
atrophy from PD.Neurology. 2002 Feb 26;58(4):575-80.
 Neurodegenerativ - DWI
Scherfler C, Donnemiller E, Schocke M, Dierkes K, Decristoforo C,
Oberladstatter M, Kolbitsch C, Zschiegner F, Riccabona G, Poewe W, Wenning G.Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT.Neuroimage. 2002 Sep;17(1):128-41.


Klinische Neurodegenerationsforschung -  EU Projekte


(European Multi System Atrophy Study Group)

Patientenregister (für neuroprotektive Studien), prospektive MSA-Progressionstudie (Natural History/Dysautonomie/MRI), DNA-Bank



Das europäische kooperative Netzwerk für Forschung, Diagnostik und Therapie bei Morbus Parkinson, EuroPa, soll bestehende Kompetenzen für klinische Parkinson-Forschung europaweit bündeln und koordinieren.


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