JPND LOss of neurotrophic factors in neurodegenerative DEmentias: Back to the crossroads of proteins (LODE)

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Neurodegenerative diseases such as Alzheimer's and Parkinson's disease are very common in our society but how they develop and what we can do to treat them is not yet clear. Indeed no cure for these diseases is available. What is known is that some proteins in these diseases form abnormal aggregates that are associated with the death of the neuronal cells and disruption of the network in which neurons are integrated, leading to memory loss (like in Alzheimer's disease) or movement problems (like in Parkinson's disease). Exosomes are small vesicles that carry molecules between cells, and are very important in maintaining communication between neurons, especially when their networks are interrupted. We propose that ,the failure of exosomes to form and carry these molecules contributes to loss of neurons and disease. Neurons are supported by growth factors which are carried by exosomes, while exosome production in turn can depend on these growth factors but the mutual relationship between exosomes and growth factors is not well understood. The aim of this application is to clarify this relationship and exploit our findings to deliver growth factors that protect and support the neurons. To achieve these aims, we will examine the presence of these growth factors in exosomes and see if the deficiency can be overcome by delivering the growth factors using nanoparticles to human neurons from diseased individuals, transgenic mouse models of disease and test if the deficiency in patients with the disease. The results will help to shed light on new mechanisms contributing to neurodegeneration and may also unmask novel disease markers besides new targets for intervention.