Hyposmia in Parkinson's disease: Localization, molecular causes of neuronal dysfunction and circuit homeostasis

• Applicant: Dr. Ulrike Pech
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391496227

Parkinson's disease (PD) is the worldwide second most common neurodegenerative disease. An early and prominent symptom of PD is the impaired ability to smell (hyposmia), occurring in both idiopathic and pathogenetic forms. However, neither is the affected neuronal substrate underlying hyposmia known, nor are the causal impairments described. In this proposal, I present a research plan to address these open questions. As frequency and symptoms of olfactory dysfunction are shared between idiopathic and pathogenetic PD, I aim to study the genetic (familial) forms of PD to reveal mechanisms of hyposmia across PD in general. To do so, I have created a newly established isogenic collection of Drosophila Parkinson models. The fly model allows for large screens and an unparalleled access to each neuron in the brain. I aim to use this collection to reveal the common underlying olfactory neuronal substrate that is disrupted across different genetic causes of Parkinson’s disease and to identify the nature of the disruption in these neurons. In the second phase I aim to identify the mechanisms by which the respective neuronal circuits compensate molecular dysfunction. Both the genes known to cause PD as well as cardinal features of olfactory circuits are well conserved across species. Therefore I will be able to reveal key features of olfactory dysfunction in PD with the long-term perspective of identifying targets of a therapeutic strategy for humans.

• DFG Programme: Research Fellowships
• International Connection: Belgium
• Host: Professor Patrik Verstreken, Ph.D.