Liliane Tenenbaum

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Dr Liliane Tenenbaum

Senior Lecturer
Group Leader
Laboratoire de neurothérapies et neuromodulation - LNTM
liliane.tenenbaum@chuv.ch

Keywords: Parkinson’s disease, Neuroprotection, Targeted and inducible gene transfer, GDNF, Neuroinflammation, Tollip

Research interests

Neuroprotective gene therapy for Parkinson’s disease
> Drug-inducible AAV vectors.
> Mechanism of GDNF neuroprotective versus neurochemical effects.

Sensing and reducing brain inflammatory responses
> Modulators of neuroinflammatory signalling.

Laboratory’s activity

Drug-inducible neuroprotective gene therapy for Parkinson’s disease (PD)

On-going gene therapy clinical trials offer efficient but uncontrolled expression of therapeutic transgenes. However, long-term, high-dose or off-target neurotrophic factors administration induces adverse effects. Our laboratory develops inducible adeno-associated viral (AAV) vectors allowing to administer glial cell line-derived neurotrophic factor (GDNF) intracerebrally, following a time- and dose-dependent regimen. Our current project consists in targeting GDNF transgene expression in specific neuronal subpopulations in order to avoid off-target effects.

Modulation of neuroinflammation

Increasing evidence suggests that chronic neuroinflammation as well as misfolded alpha-synuclein accumulation both play important roles in PD. Toll-interacting protein (Tollip) is a modulator of inflammatory cascades. Interestingly, it also acts as an adaptor in complexes that mediate autophagy of aggregated proteins. We have shown that Tollip was particularly abundant in substantia nigra dopaminergic neurons. In addition, the response to an inflammatory challenge in the midbrain was exacerbated in tollip-deficient mice. Our hypothesis is that Tollip, by reducing neuroinflammation and preventing alpha-synuclein oligomerization, could be neuroprotective for dopaminergic neurons.

 

ORCID: 0000-0003-4619-9660

Publications: Unisciences

UNIL: www.unil.ch/lcmn/home/menuinst/research-groups/gene-transfer-for-parkinsons.html

 

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