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NPlast - A neuroscience school that aims to preserve and restore neuroplasticity in brain disorders

Final Report Summary - NPLAST (NPlast - A neuroscience school that aims to preserve and restore neuroplasticity in brain disorders)

Brain disorders impose an increasing economical and social burden in the member states of the European Union (EU). For most neurodegenerative diseases and many neuropsychiatric disorders no efficient treatment is available and no cure exists. In the next coming years the number of particularly elderly people suffering from brain disorders will tremendously increase. The complexity of these diseases requires a more integrative view of the multiple interactions between genes and environment, synaptic processes and neuronal circuitry. NPlast will train young neuroscientists in relevant techniques by bringing together expertise from different areas of neuroscience that merge in a highly multidisciplinary research and training program.
The NPlast consortium consists of four partners from the private and eight partners from the public sector and provides a research training program for fifteen young scientists. The program covers a broad spectrum of disorders and interventions ranging from synaptopathies and trafficking deficiencies to Alzheimer’s disease, and from altering gene expression programs to manipulations of the extracellular matrix of the brain to preserve or restore synaptic function. The key objective of the NPlast training network is to investigate neuroplastic principles that can preserve or restore function and that can be used to ‚rejuvenate’ the brain in the elderly as well as to treat neuropsychiatric conditions in adults. Further information can be found on the website of the ITN (
During the complete period we have made major progress towards a better understanding on how synaptic processes are altered in neurodegenerative diseases like Alzheimer's disease and we could show that posttranslational modification of the so-called Amyloid-beta (Abeta) peptide, a causative agent in Alzheimer’s disease, results in peptides that influence synaptic function by vastly different means. In addition we identified mechanisms in the regulation of gene expression that maintain neurodegenerative disorders like Huntington’s disease. Further work was devoted to the analysis of transcriptional regulation in addiction and also novel targets for pharmacological interventions in synaptic dysfunction in neuropsychiatric disorders were identified.
An impressive number of novel tools were generated that allow visualization of dynamic processes in neurons and we applied these novel techniques to learn more about synaptic function in health and disease. In a multidisciplinary approach we have used discrete mathematics to generate large-scale signalling networks in collaboration with several partners of the consortium. This inspires neurobiologists to ask new questions and it will have valuable potential in foreseeing the effects of network modifications that are not obvious prima facie. A further highlight of the work done so far concerns the identification of signalling pathways that establish and maintain brain disease states by altering gene expression programs. In truly multidisciplinary work we have identified novel mechanisms that change the expression of genes in disease states. Finally, NPlast has analysed cellular plasticity and gene expression profiles in animal models to identify disease mechanisms. NPlast students were trained on projects which contributed to interventions that aim to preserve or even restore synaptic function in disease. These interventions will probably delay the onset or might even now provide first steps in direction of a cure for such disorders.