As the acronym “CrossSeeds” implies, this project 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.

A traditional view on these devastating disorders focuses on individual, disease-specific enzymes and / or aggregating proteins contributing to aspects of neuropathology.

The CrossSeeds consortium combines experimental approaches from fundamental, pre-clinical and clinical neuroscience with computational approaches to identify cross-disease pathways leading to pathogenic protein aggregation.

All three diseases have at least one feature in common: Aggregation of pathogenic proteins associated with neurodegeneration. For example, Abeta peptides modified by glutaminyl cyclase (QC) to form pyroglutamate (pGlu) act as seed for protein aggregation and provoke neurodegeneration in AD. As shown in preliminary experiments the AD-specific peptide pGlu-Abeta is also present in Lewy bodies of substantia nigra dopaminergic neurons of PD subjects and induces cross-seeding of alpha-synuclein. Our research expects to substantiate the hypothesis that post-translational modifications induce or enhance the amyloidogenic properties of Abeta, alpha-synuclein and huntingtin.

The consortium was established to combine disease-specific and methodological skills of European Research groups with and outstanding publication record and impressive funding history by national and European Research Institutions. In particular, experts in the field of Alzheimer’s disease (Prof. Dr. Steffen Roßner, Germany), Parkinson’s disease (Prof. Dr. Stéphane Hunot, France), Huntington’s disease (Prof. Dr. Stephan von Hörsten, Germany), computational network analyses (Prof. Dr. Jan G. Bjaalie, Norway) and protein aggregation and preclinical development (Prof. Dr. Hans-Ulrich Demuth, Germany) will join forces to dissect common pathological mechanisms of protein aggregation in three major neurodegenerative disorders affecting a large – and increasing – European population.

The expected results will be of tremendous value for further basic and clinical research and for the development of novel therapeutic strategies to treat the diseases addressed. Scientific results of the individual research groups will be put in context with each other to achieve an unprecedented gain of knowledge on cross-disease mechanisms of pathogenic protein deposition.

Funding

JPND logo BMBF logo

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases. JPND aims to increase coordinated investment between participating countries in research aimed at finding causes, developing cures, and identifying appropriate ways to care for those with neurodegenerative diseases – www.jpnd.eu