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Synaptic circuit protection in Alzheimers’s disease (AD) and Huntingtion’s disease (HD): BDNF/TrkB and Arc signaling as rescue factors


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European Countries Involved
Alzheimer´s (AD) and Huntington´s disease (HD) result from the erroneous communication of neurons at synapses in different brain areas (neocortex, hippocampus, striatum). The protein BDNF regulates synaptic communication under healthy conditions. However, insufficient release of BDNF from neurons and defective BDNF signaling in target neurons contribute to cellular malfunctions in AD and HD. Although they are essential to the development of effective therapies, the underlying molecular mechanisms for deficits in synaptic communication in these diseases are not understood. CircProt will employ AD and HD mouse models to investigate the synapse communication deficits for both diseases. Using microscopy methods to investigate BDNF trafficking and release, electrophysiological recordings to check for altered synaptic activity, structural analysis of synaptic contact points (spines), analysis of intracellular protein networks, and behavioral analysis of memory dysfunction (AD) and motor/ cognitive deficits (HD), CircProt will disentangle the role of defective BDNF function in both diseases. Dis-eased mice will be treated with drugs that either speed up BDNF release or boost BDNF signaling to investi-gate how drug treatment ameliorates synaptic communication. Computational modeling of neuronal cir-cuits will assist in the quantitative analysis of improved synaptic function in response to treatment. Thus, CircProt will aid the development of effective future therapies for both diseases.
Project partners
Otto-von-Guericke-University Magdeburg
University of Helsinki
University of Bergen
University Grenoble Alpes
Heinrich-Heine-University Düsseldorf
National Research Council
Institute of Biophysics
University of Milano
Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).