completed

Search for new therapies against Parkinson's disease using zebrafish

The aim of the project is to develop zebrafish models to understand Parkinson's disease and identify novel therapeutic targets and drugs

Start – End dates: 07/01/20 – 06/01/23

Project reference: Doctorados Industriales 2017 (DI-17-09642)

Total budget: 110,000€

Financed by: State Research Agency under the Ministry of Science, Innovation and Universities, Spain

Financed by MICIU/AEI/10.13039/501100011033

Partners: Intelligent Pharma & Universidad Pompeu Fabra (UPF), Barcelona

Summary:

The term “neurodegenerative disorder” groups those diseases in which the nervous system suffers progressive deterioration, manifested by a cognitive dysfunction, motor decline, and changes in behaviour. Among those, Parkinson’s disease (PD) represents the second most common neurodegenerative disease. The aetiology of PD entails a complex interaction of environmental and genetic factors. The latter accounts for 10-20% of patients, with different genes identified as a driven cause. The discovery of new biomarkers is of paramount importance to develop effective drug therapies, as nowadays PD cannot be prevented, delayed or cured. Therefore, it is of fundamental importance to generate animal models that resemble the onset, progression, and symptomatology of the pathology in order to shed light on the pathological mechanisms of this debilitating disease. For this reason, the main objective of this Doctorado Industrial is to generate a combination of genetic and pharmacological zebrafish models of PD to utilise as a means for identifying novel therapeutic targets and drugs that might have a positive impact in PD treatment. The results of this project show how the selected genetic models – overexpression of park1/snca and loss-of- function of park2/parkin, park6/pink1, park7/DJ-1, and park8/lrrk2 – display a subset of phenotypes that agree with those observed in PD patients, namely, defects in locomotion and loss of dopaminergic neurons. In addition, transcriptomic data, derived from neurons isolated from the same genetic models, show multiple dysregulated genes previously associated with Parkinson or with Parkinson related hallmarks, such as mitochondria dysfunction, inflammation or apoptosis.