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Laboratory for Translational Neurodegeneration Research

Mission Statement

Our research focuses on basic molecular mechanisms, biomarker discovery and new treatment options for neurodegenerative diseases with special emphasis on α-synucleinopathies including Parkinson’s disease (PD) and Multiple System Atrophy (MSA). We investigate the role of oligomeric α-synuclein to trigger disease-specific phenotypes, the effects of exogenous stress factors and epigenetic modulation in models of α-synucleinopathy, the involvement of glial cells in PD and MSA, and the neuroinflammatory mechanisms associated with α-synuclein pathology. Through preclinical screening and target validation for disease modification, we aim to provide rationale for clinical trials in PD and MSA.

 

People

Univ.-Prof. Nadia Stefanova MD, PhD, DSc
Head of Laboratory
nadia.stefanova@i-med.ac.at
Antonio Heras-Garvin PhD
PostDoc
antonio.heras@i-med.ac.at
Miguel Lemos PhD
PostDoc
miguel.lemos@i-med.ac.at
Alain Ndayisaba MD
PhD Student
alain.ndayisaba@student.i-med.ac.at
Martina Wick MSc
Research Assistant
martina.wick@i-med.ac.at
Kathrin Juliana Vouk
Bachelor Student
kathrin.vouk@student.i-med.ac.at

Former members:

Katja Malfertheiner BSc
Lisa Fellner PhD
Claudio Schmidt MSc
Violetta Refolo PhD
Tamina Weiss BSc
Marcos Herrera-Vaquero PhD
Lorenz Härtner PhD
Serena Venezia PhD
Martin Kallab MD
Edith Sturm PhD
Karin Spiss
Christine Kaindlstorfer MD PhD
Florian Krismer MD PhD
Daniela Kuzdas-Wood PhD
Dominik Brück MSc
Michael Lohmüller BSc
Christine Mantinger MD
Patrick Sommer MD
Melanie Premstaller MD
Philipp Hockl MD
Monika Hainzer
Yuntao Li MD 
Sonya Neto PhD
Sylvia Stemberger PhD
Philipp Fuchs MD
Julia Kuen MD
Ankit Gupta
Undine Hauser MD
Lucas Mangard MD
Violeta Staeva MD
Harald Granbichler
Laura Mantoan MD
Monika Mitschnigg MD
Theron Sather MD
Sonja Scholz MD
Zoe Puschban MD
Christoph Scherfler MD

Research Focus

Molecular Mechanisms in Synucleinopathies

Modeling

Signs of early cellular dysfunction in multiple system atrophy.
Induced pluripotent stem cells in multiple system atrophy: recent developments and scientific challenges. 

Progressive striatonigral degeneration in a transgenic mouse model of multiple system atrophy: translational implications for interventional therapies. 
Distinct Parameters in the EEG of the PLP α-SYN Mouse Model for Multiple System Atrophy Reinforce Face Validity. 
Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype. 
Intact olfaction in a mouse model of multiple system atrophy.
Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: experimental evidence. 
In vitro models of multiple system atrophy. 
Animal models of multiple system atrophy. 
Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy). 
Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy). 
Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells. 
Glial cell death induced by overexpression of alpha-synuclein. 

Exogenous stress and epigenetic modulation

High-salt diet does not boost neuroinflammation and neurodegeneration in a model of α-synucleinopathy.
Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy. 

Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications. 
Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity. 
Multiple system atrophy: genetic or epigenetic? 
Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. 
Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. 

Glial responses and neuroinflammation

Signs of Chronic Hypoxia Suggest a Novel Pathophysiological Event in α-Synucleinopathies.
Neuroinflammation and Glial Phenotypic Changes in Alpha-Synucleinopathies.

Toll-like receptor 4 stimulation with monophosphoryl lipid A ameliorates motor deficits and nigral neurodegeneration triggered by extraneuronal α-synucleinopathy. 
Glia and alpha-synuclein in neurodegeneration: A complex interaction.   
Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. 
The role of glia in α-synucleinopathies. 
Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons. 
Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts. 
Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. 
Tumor necrosis factor-alpha-induced cell death in U373 cells overexpressing alpha-synuclein. 

 

Biomarker Discovery in Synucleinopathies

Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. 
Alpha-synuclein immunoreactivity patterns in the enteric nervous system. 

New Therapeutics for Synucleinopathies

Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance
The molecular tweezer CLR01 reduces aggregated, pathologic, and seeding-competent α-synuclein in experimental multiple system atrophy

Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. 
Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy. 
Translational therapies for multiple system atrophy: Bottlenecks and future directions. 
Failure of Neuroprotection Despite Microglial Suppression by Delayed-Start Myeloperoxidase Inhibition in a Model of Advanced Multiple System Atrophy: Clinical Implications. 
Myeloperoxidase inhibition ameliorates multiple system atrophy-like degeneration in a transgenic mouse model. 
Rasagiline is neuroprotective in a transgenic model of multiple system atrophy.