search_icon 

close_icon

search_icon  

search_icon  

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
Patrick Bachmann
Medical Diploma Student
patrick.bachmann@student.i-med.ac.at

Former members

 

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.