Project: Mechanisms of pathogenic protein cross-seeding in neurodegenerative disorders
This proposal is based on the hypothesis that a number of brain disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) share common pathogenic mechanisms leading to neurodegeneration. Here, we combine experimental approaches of pre-clinical and clinical neuroscience with computational approaches to identify cross-disease pathways leading to pathogenic protein aggregation. In particular, we focus on (common) post-translational protein modifications such as pyroglutamate (pGlu) formation that induce pathogenic folding of proteins and, potentially, cross-seeding. We intend to address 4 specific aims: (i) characterize the cross-seeding of capacity of pGlu-Abeta, alpha-synuclein and huntingtin peptides in vitro. (ii) investigate the co-occurrence of these pathogenic peptides in brain structures affected in AD, PD and HD and in animal models thereof. (iii) generate a map of pathogenic protein (co)-aggregates in human brain and respective animal models and develop a computer-based model of neuronal circuits affected by such protein aggregates in individual clinical conditions. This map will be uploaded to an open access public database that allows comments, correction and addition of data from others. (iv) interfere with pathogenic protein aggregation by vaccination against disease-related epitopes in animal models to delineate novel therapeutic strategies.
| Acronym | CrossSeeds (Reference Number: JPND_CD_FP-688-052) |
| Duration | 01/01/2015 - 01/01/2018 |
| Project Topic | Neurodegenerative disease |
| Website | visit project website |
| Network | JPND |
| Call | A call for European research projects for cross-disease analysis of pathways related to neurodegenerative diseases |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Fraunhofer Gesellschaft zur Förderung der Angewandten Forschung e.V. | Coordinator | Germany |
| 2 | Universität Leipzig (ULEI) | Partner | Germany |
| 3 | University of Oslo (UiO) | Partner | Norway |
| 4 | University of Erlangen-Nürnberg (FAU) | Partner | Germany |
| 5 | Institut du Cerveau et de la Moelle epiniere (ICM) | Partner | France |